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Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock

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Recent Advances on Model Hosts

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 710))

Abstract

Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults.

As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our attempts to create “pro-survival and anti-inflammatory phenotype” in various models of hemorrhagic shock and septic shock.

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Abbreviations

ASK1:

Apoptosis signal regulating kinase 1

BAD:

Bcl-xl/Bcl-2 associated death promoter

Bcl-2:

B-cell lymphoma 2

β2-AR:

Beta2-adrenergic receptor

BMP7:

Bone morphogenetic protein 7

CASP:

Colon ascendant stent peritonitis

CBP:

Cyclic AMP (cAMP) response element binding protein (CREBP) binding protein

CCL2:

Chemokine (C-C motif) ligand 2

CINC:

Cytokine-induced neutrophil chemoattractant

CLP:

Cecal ligation puncture

DAMPs:

Damage-associated molecular patterns

DNA:

Deoxyribonucleic acid

DUSP5:

Dual specificity protein phosphatase 5

ELISA:

Enzyme-linked immunosorbent assay

ER:

Endoplasmic reticulum

ERK:

Extracellular signal regulated kinase

F-actin:

Filamentous actin

FWB:

Fresh whole blood

GSK-3β:

Glycogen synthase kinase-3β

h:

Hour

H:

Histone

HATs:

Histone acetylases

HDA1:

Histone deacetylase A1

HDACs:

Histone deacetylases

HDACI:

Histone deacetylase inhibitors

HMGB1:

High mobility group box 1

HS:

Hemorrhagic shock

Hsp 70:

Heat shock protein 70

Hsp 90:

Heat shock protein 90

ICAM-1:

Intercellular adhesion molecule-1

IFN:

Interferon

IGF-1:

Insulin-like growth factor 1

IKK:

IκB kinase

IL:

Interleukin

IRAK 1:

Interleukin-1 receptor associated kinase 1

IRF3:

Interferon regulatory factor 3

IV:

Intravenous (injection into a vein)

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MAGUK:

Membrane-associated guanylate kinase

MAP:

Mean arterial pressure

MAPK:

Mitogen-activated protein kinase

MEF2:

Myocyte enhancer factor 2

MKP-1:

MAP kinase phosphatase 1

MMTV:

Mouse mammary tumor virus

MODS:

Multi-organ dysfunction syndrome

MPO:

Myeloperoxidase

MSK1:

Mitogen and stress-activated protein kinase 1

MyD88:

Myeloid differentiation factor 88

NAD:

Nicrotinamide adenine dinucleotide

NF-κB:

Nuclear factor kappa B

PAMPs:

Pathogen-associated molecular patterns

PCAF:

p300/CREB-binding protein-associated factor

PCI:

Peritoneal contamination and infection

p300:

p300 histone acetyl transferase

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator-1α

PI3K:

Phosphoinositide 3 kinase

PIP2:

Phosphatidylinositol 4,5-bisphosphate

PIP3:

Phosphatidyl-inositol,3,4,5 triphosphate

PKB:

Protein kinase B

PTEN:

Phosphatase and tensin homolog

ROS:

Reactive oxygen species

RSK2:

Ribosomal S6 kinase 2

SAHA:

Suberoylanilide hydroxamic acid

SEK:

Stress-activated protein kinase (SAPK)/extracellular signal-regulated kinase (ERK) kinase

SIRS:

Systemic inflammatory response syndrome

SIRT:

Sirtuins

SMA:

Superior mesenteric artery

RT-PCR:

Reverse transcription polymerase chain reaction

TBP2:

Trx binding protein 2

TFs:

Transcription factors

TJ:

Tight junction

TLR4:

Toll-like receptor 4

TNF-α:

Tumor necrosis factor α

TRAF6:

TNF receptor associated factor 6

TRB3:

Tribbles 3

Trx:

Thioredoxin

TSA:

Trichostatin A

VCAM-1:

Vascular cell adhesion molecule-1

VPA:

Valproic acid

VSMCs:

Vascular smooth muscle cells

WT:

Wild type

References

  • Adam E, Quivy V, Bex F et al (2003) Potentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase inhibitors is associated with a delayed cytoplasmic reappearance of I kappa B alpha. Mol Cell Biol 23(17):6200–6209

    Article  PubMed  CAS  Google Scholar 

  • Alam HB, Shuja F, Butt MU, Duggan M, Li Y, Zacharias N, Fukudome EY, Liu B, Demoya M, Velmahos GC (2009) Surviving blood loss without transfusion in a swine poly-trauma model. Surgery 146(2):325–333

    Article  PubMed  Google Scholar 

  • Andreasen AS, Krabbe KS, Krogh-Madsen R et al (2008) Huamn endotoxemia as a model of systemic inflammation. Curr Med Chem 15(17):1697–1705

    Article  PubMed  CAS  Google Scholar 

  • Ashburner BP, Westerheide SD, Baldwin AS Jr (2001) The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol Cell Biol 21(20):7065–7077

    Article  PubMed  CAS  Google Scholar 

  • Avery J, Etzion S, DeBosch BJ et al (2010) TRB3 function in cardiac endoplasmic reticulum stress. Circ Res 106(9):1516–1523

    Article  PubMed  CAS  Google Scholar 

  • Avila AM, Burnett BG, Taye AA et al (2007) Trichostatin A increases SMN expression and survival in amousemodel of spinal muscular atrophy. J Clin Invest 117:659–671

    Article  PubMed  CAS  Google Scholar 

  • Ayala A, Chung CS, Lomas J et al (2002) Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Am J Pathol 161(6):2283–2294

    Article  PubMed  CAS  Google Scholar 

  • Baker JW, Deitch EA, Li M et al (1988) Hemorrhagic shock induces bacterial translocation from the gut. J Trauma 28(7):896–906

    Article  PubMed  CAS  Google Scholar 

  • Bauhofer A, Lorenz W, Kohlert F et al (2006) Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis. Crit Care Med 34(3):778–784

    PubMed  CAS  Google Scholar 

  • Beere HM, Wolf BB, Cain K et al (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2(8):469–475

    Article  PubMed  CAS  Google Scholar 

  • Bhatia M, He M, Zhang H et al (2009) Sepsis as a model of SIRS. Front Biosci 14:4703–4711

    Article  PubMed  CAS  Google Scholar 

  • Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81(1):1–5

    Article  PubMed  CAS  Google Scholar 

  • Blanchard F, Chipoy C (2005) Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov Today 10(3):197–204

    Article  PubMed  CAS  Google Scholar 

  • Botha AJ, Moore FA, Moore EE et al (1995) Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma 39(3):411–417

    Article  PubMed  CAS  Google Scholar 

  • Buczek-Thomas JA, Hsia E, Rich CB et al (2008) Inhibition of histone acetyltransferase by glycosaminoglycans. J Cell Biochem 105(1):108–120

    Article  PubMed  CAS  Google Scholar 

  • Butler LM, Zhou X, Xu WS et al (2002) The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci USA 99(18):11700–11705

    Article  PubMed  CAS  Google Scholar 

  • Camelo S, Iglesiuas AH, Hwang D et al (2005) Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis. J Neuroimmunol 164:10–21

    Article  PubMed  CAS  Google Scholar 

  • Cao W, Bao C, Padalko E, Lowenstein CJ (2008) Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling. J Exp Med 205(6):1491–1503

    Article  PubMed  CAS  Google Scholar 

  • Carey N, La Thangue NB (2006) Histone deacetylase inhibitors: gathering pace. Curr Opin Pharmacol 6:369–375

    Article  PubMed  CAS  Google Scholar 

  • Cha JH (2000) Transcriptional dysregulation in Huntington’s disease. Trends Genet 23(9):387–392

    CAS  Google Scholar 

  • Champion HR, Bellamy RF, Roberts CP, Leppaniemi A (2003) A profile of combat injury. J Trauma 5:S13–S19

    Google Scholar 

  • Chang KT, Min KT (2002) Regulation of lifespan by histone deacetylase. Ageing Res Rev 1(3):313–326

    Article  PubMed  CAS  Google Scholar 

  • Chang JG, Hsieh-Li HM, Jong YJ et al (2001) Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci USA 98:9808–9813

    Article  PubMed  CAS  Google Scholar 

  • Chaudry IH, Ayala A (1993) Mechanism of increased susceptibility to infection following hemorrhage. Am J Surg 165(2A Suppl):59S–67S

    Article  PubMed  CAS  Google Scholar 

  • Chen LF, Greene WC (2004) Shaping the nuclear action of NF-kappaB. Nat Rev Mol Cell Biol 5(5):392–401

    Article  PubMed  CAS  Google Scholar 

  • Chen LF, Wu Y, Greene WC (2002) Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB. EMBO J 21(23):6539–6548

    Article  PubMed  CAS  Google Scholar 

  • Cheng Q, McKeown SJ, Santos L et al (2010) Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules. J Immunol 185:1238–1247

    Article  PubMed  CAS  Google Scholar 

  • Chesley A, Lundberg MS, Asai T, Xiao RP, Ohtani S, Lakatta EG, Crow MT (2000) The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3’-kinase. Circ Res 87:1172–1179

    PubMed  CAS  Google Scholar 

  • Chi H, Flavell RA (2008) Acetylation of MKP = 1 and the control of inflammation. Sci Signal 1(41):pe44

    Article  PubMed  CAS  Google Scholar 

  • Choi Y, Park SK, Kim HM et al (2008) Histone deacetylase inhibitor KBH-A42 inhibits cytokine production in RAW 264.7 macrophage cells and in vivo endotoxemia model. Exp Mol Med 40(5):574–581

    Article  PubMed  CAS  Google Scholar 

  • Choudhry MA, Bland KI, Chaudry IH (2007) Trauma and immune response-effect of gender differences. Injury 38(12):1382–1391

    Article  PubMed  Google Scholar 

  • Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT (2009) Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 32(11):591–601

    Article  PubMed  CAS  Google Scholar 

  • Dangond F, Gullans SR (1998) Differential expression of human histone deacetylase mRNAs in response to immune cell apoptosis induction by trichostatin A and butyrate. Biochem Biophys Res Commun 247:833–837

    Article  PubMed  CAS  Google Scholar 

  • de Ruijter AJ, van Gennip AH, Caron HN et al (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370(Pt 3):737–749

    PubMed  Google Scholar 

  • DeBosch B, Sambandam N, Weinheimer C, Courtois M, Muslin AJ (2006) Akt2 regulates cardiac metabolism and cardiomyocyte survival. J Biol Chem 281:32841–32851

    Article  PubMed  CAS  Google Scholar 

  • Deitch EA (1992) Multiple organ failure. Pathophysilogy and potential future therapy. Ann Surg 216:117–134

    Article  PubMed  CAS  Google Scholar 

  • Deitch EA (2001) Role of the gut lymphatic system in multiple organ failure. Curr Opin Crit Care 7(2):92–98

    Article  PubMed  CAS  Google Scholar 

  • Deitch EA, Bridges W, Ma L et al (1990) Hemorrhagic shock-induced bacterial translocation: the role of neutrophils and hydroxyl radicals. J Trauma 30:942–952

    Article  PubMed  CAS  Google Scholar 

  • Deitch EA, Xu D, Kaise VL (2006) Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review. Front Biosci 11:520–528

    Article  PubMed  CAS  Google Scholar 

  • Deng WG, Wu KK (2003) Regulation of inducible nitric oxide synthase expression by p300 and p50 acetylation. J Immunol 171(12):6581–6588

    PubMed  CAS  Google Scholar 

  • Dokmanovic M, Clarke C, Marks PA (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5(10):981–989

    Article  PubMed  CAS  Google Scholar 

  • Du K, Herzig S, Kulkarni RN et al (2003) TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300:1574–1577

    Article  PubMed  CAS  Google Scholar 

  • Esrig BC, Frazee L, Stephenson SF et al (1977) The predisposition to infection following hemorrhagic shock. Surg Gynecol Obstet 144(6):915–917

    PubMed  CAS  Google Scholar 

  • Fan J (2010) TLR cross-talk mechanism of hemorrhagic shock-primed pulmonary neutrophil infiltration. Open Crit Care Med J 2:1–8

    Article  PubMed  CAS  Google Scholar 

  • Fan J, Marshall JC, Jimenez M et al (1998) Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide. J Immunol 161:440–447

    PubMed  CAS  Google Scholar 

  • Fan J, Kapus A, Li YH et al (2000) Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor. Am J Respir Cell Mol Biol 22(4):412–421

    PubMed  CAS  Google Scholar 

  • Faraco G, Pancani T, Formentini L et al (2006) Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol Pharmacol 70(6):1876–1884

    Article  PubMed  CAS  Google Scholar 

  • Ferrante RJ, Kubilus JK, Lee J et al (2003) Histone deactylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice. J Neurosci 23:9418–9427

    PubMed  CAS  Google Scholar 

  • Fink MP, Delude RL (2005) Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level. Crit Care Clin 21(2):177–196

    Article  PubMed  CAS  Google Scholar 

  • Fukudome EY, Kochanek AR, Li Y et al (2010) Pharmacologic resuscitation promotes survival and attenuates hemorrhage-induced activation of extracellular signal-regulated kinase ½. J Surg Res 163(1):118–126

    Article  PubMed  CAS  Google Scholar 

  • Fukudome EY, Li Y, Kochanek AR (2011) Pharmacologic resuscitation decreases circulating CINC-1 levels and attenuates hemorrhage-induced acute lung injury. Surgery in press

    Article  PubMed  CAS  Google Scholar 

  • Gao T, Newton AC (2002) The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C. J Biol Chem 277(35):31585–31592

    Article  PubMed  CAS  Google Scholar 

  • Gill R, Tsung A, Billiar T (2010) Linking oxidative stress to inflammation: toll-like receptors. Free Radical Biol Med 48:1121–1132

    Article  CAS  Google Scholar 

  • Gonzales E, Chen H, Munuve R, Mehrani T, Britten-Webb J, Nadel A, Alam HB, Wherry D, Burris D, Koustova E (2006) Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones. Shock 25(4):395–401

    Article  PubMed  CAS  Google Scholar 

  • Gonzales E, Chen H, Munuve RM, Mehrani T, Nadel A, Koustova E (2008) Hepatoprotection and lethality rescue by histone deacetylase inhibitor valproic acid in fatal hemorrhagic shock. J Trauma 65(3):554–565

    Article  PubMed  CAS  Google Scholar 

  • Gotoh T, Terada K, Oyadomari S et al (2004) hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ 11(4):390–402

    Article  PubMed  CAS  Google Scholar 

  • Granger A, Abdullah I, Huebner F, Stout A, Wang T, Huebner T, Epstein JA, Gruber PJ (2008) Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. FASEB J 22:3549–3560

    Article  PubMed  CAS  Google Scholar 

  • Haggarty SJ, Koeller KM, Wong JC et al (2003) Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 100(8):4389–4394

    Article  PubMed  CAS  Google Scholar 

  • Harlan JH, Winn RK (2002) Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy. Crit Care Med 30(5):S214–S219

    Article  PubMed  CAS  Google Scholar 

  • Hassoun HT, Kone BC, Mercer DW et al (2001) Post-injury multiple organ failure: the role of the gut. Shock 15(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132(3):344–362

    Article  PubMed  CAS  Google Scholar 

  • Heumann D, Roger T (2002) Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta 323(1–2):59–72

    Article  PubMed  CAS  Google Scholar 

  • Hierholzer C, Billiar TR (2001) Molecular mechanisms in the early phase of hemorrhagic shock. Langenbecks Arch Surg 386:302–308

    Article  PubMed  CAS  Google Scholar 

  • Hockly E, Richon VM, Woodman B et al (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in amousemodel of Huntington’s disease. Proc Natl Acad Sci USA 100:2041–2046

    Article  PubMed  CAS  Google Scholar 

  • Hu E, Dul E, Sung CM et al (2003) Identification of novel isoform-selective inhibitors within class I histone deacetylases. J Pharmacol Exp Ther 307(2):720–728

    Article  PubMed  CAS  Google Scholar 

  • Huang N, Katz JP, Martin DR et al (1997) Inhibition of IL-8 gene expression in Caco-2 cells by compounds which induce histone hyperacetylation. Cytokine 9(1):27–36

    Article  PubMed  CAS  Google Scholar 

  • Inan MS, Rasoulpour RJ, Yin L et al (2000) The luminal short-chain fatty acid butyrate modulates NF-kappaB activity in a human colonic epithelial cell line. Gastroenterology 118(4):724–734

    Article  PubMed  CAS  Google Scholar 

  • Inoue K, Kobayashi M, Yano K et al (2006) Histone deacetylase inhibitor reduces monocyte adhesion to endothelium through the suppression of vascular cell adhesion molecule-1 expression. Arterioscler Thromb Vasc Biol 26(12):2652–2659

    Article  PubMed  CAS  Google Scholar 

  • Jaattela M, Wissing D, Kokholm K et al (1998) Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases. EMBO J 17(21):6124–6134

    Article  PubMed  CAS  Google Scholar 

  • Kelly WK, Marks PA (2005) Drug insight: Histone deacetylase inhibitors – development of the new targeted anticancer agent suberoylanilide hydroxamic acid. Nal Clin Pract Oncol 2(3):150–157

    Article  CAS  Google Scholar 

  • Kiernan R, Bres V, Ng RW et al (2003) Post-activation turn-off of NF-kappaB-dependent transcription is regulated by acetylation of p65. J Biol Chem 278(4):2758–2766

    Article  PubMed  CAS  Google Scholar 

  • Kim AJ, Shi Y, Austin RC et al (2005) Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 118:89–99

    Article  PubMed  CAS  Google Scholar 

  • Kim KH, Oudit GY, Backx PH (2008) Erythropoietin protects against doxorubicin-induced cardiomyopathy via a phosphatidylinositol 3-kinase-dependent pathway. J Pharmacol Exp Ther 324:160–169

    Article  PubMed  CAS  Google Scholar 

  • Kim K, Li Y, Jin G et al. (2011) Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion. Resuscitation in press

    Article  PubMed  CAS  Google Scholar 

  • Kishimoto H, Hamada K, Saunders M, Backman S, Sasaki T, Nakano T et al (2003) Physiological functions of Pten in mouse tissues. Cell Struct Funct 28:11–21

    Article  PubMed  CAS  Google Scholar 

  • Kochenek AR, Fukudome EY, Eleanor JS et al (2010) Pharmacological resuscitation attenuates MAP kinase pathway activation and pulmonary inflammation following hemorrhagic shock in rodent model. Oral presentation at the annual meeting of the American college of surgeons, October 2010

    Google Scholar 

  • Kramer OH, Gottlicher M, Heinzel T (2001) Histone deacetylase as a therapeutic target. Trends Endocrinol Metab 12(7):294–300

    Article  PubMed  CAS  Google Scholar 

  • Krishnaswamy G, Kelley J, Yerra L, Smith JK, Chi DS (1999) Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J Interferon Cytokine Res 19(2):91–104

    Article  PubMed  CAS  Google Scholar 

  • Krivoruchko A, Storey KB (2010) Epigenetics in anoxia tolerance: a role for histone deacetylase. Mol Cell Biochem 342(1–2):151–161

    Article  PubMed  CAS  Google Scholar 

  • Kucharska A, Rushworth LK, Staples C et al (2009) Regulation of the inducible nuclear dual-specificity phosphatase DUSP5 by ERK MAPK. Cell Signal 21(12):1794–1805

    Article  PubMed  CAS  Google Scholar 

  • Lane AA, Chabner BA (2009) Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 27(32):5459–5468

    Article  PubMed  CAS  Google Scholar 

  • Lee JO, Yang H, Georgescu MM et al (1999) Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 99:323–334

    Article  PubMed  CAS  Google Scholar 

  • Leoni F, Fossati G, Lewis EC et al (2005) The histone deacetylase inhibitor ITF2357 reduction of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med 11:1–15

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Liu B, Sailhamer EA, Yuan Z, Shults C, Velmahos GC, deMoya M, Shuja F, Butt MU, Alam HB (2008a) Cell protective mechanism of valproic acid in lethal hemorrhagic shock. Surgery 144(2):217–224

    Article  PubMed  Google Scholar 

  • Li Y, Yuan Z, Liu B, Sailhamer EA, Shults C, Velmahos GC, Demoya M, Alam HB (2008b) Prevention of hypoxia-induced neuronal apoptosis through histone deacetylase inhibition. J Trauma 64(4):863–870

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Liu B, Zhao H, Sailhamer EA, Fukudome EY, Zhang X, Kheirbek T, Finkelstein RA, Velmahos GC, deMoya CA, Hales RA, Alam HB (2009) Protective effect of suberoylanilide hydroxamic acid against LPS-induced septic shock in rodents. Shock 32(5):517–523

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Liu B, Fukudome EY, Kochanek AR, Finkelstein R, Chong W, Jin G, Lu J, deMoya M, Velmahos GC, Alam HB (2010a) Survival lethal septic shock without fluid resuscitation in a rodent model. Surgery 148(2):246–254

    Article  PubMed  Google Scholar 

  • Li Y, Liu B, Dillon S, Liu B et al (2010b) Identification of a novel potential biomarker in a model of hemorrhagic shock and valproic acid treatment. J Surg Res 159(1):474–481

    Article  PubMed  CAS  Google Scholar 

  • Lillig CH, Holmgren A (2007) Thioredoxin and related molecules – from biology to health and disease. Antioxid Redox Signal 9(1):25–47

    Article  PubMed  CAS  Google Scholar 

  • Lin T, Alam HB, Chen H, Britten-Webb J, Rhee P, Kirkpatrick J, Koustova E (2006) Cardiac histones are substrates of histone deacetylase activity in hemorrhagic shock and resuscitation. Surgery 139:365–376

    Article  PubMed  Google Scholar 

  • Lin T, Chen H, Koustova E, Sailhamer EA et al (2007) Histone deacetylase as therapeutic target in a rodent model of hemorrhagic shock: effect of different resuscitation strategies on lung and liver. Surgery 141(6):784–794

    Article  PubMed  Google Scholar 

  • Lomas-Niera J, Chung CS, Grutkoski PS et al (2005a) Divergent roles of murine neutrophil chemokines in hemorrhage induced priming for acute lung injury. Cytokine 31:169–179

    Article  CAS  Google Scholar 

  • Lomas-Niera JL, Perl M, Chung C et al (2005) Shock and hemorrhage: an overview of animal models. Shock 24(Suppl 1):33–39

    Article  PubMed  Google Scholar 

  • Maehama T, Dixon JE (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375–13378

    Article  PubMed  CAS  Google Scholar 

  • Mai A, Massa S, Pezzi R et al (2003) Discovery of (aryloxopropenyl) pyrrolyl hydroxyamides as selective inhibitors of class IIa histone deacetylase homologue HD1-A. J Med Chem 46(23):4826–4829

    Article  PubMed  CAS  Google Scholar 

  • Marinova Z, Ren M, Wendland JR, Leng Y, Liang MH, Yasuda S, Leeds P, Chuang DM (2009) Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation. J Neurochem 111(4):976–987

    Article  PubMed  CAS  Google Scholar 

  • Marks PA, Dokmanovic M (2005) Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs 14:1497–1511

    Article  PubMed  CAS  Google Scholar 

  • Marumo T, Hishikawa K, Yoshikawa M et al (2008) Epigenetic regulation of BMP7 in the regenerative response to ischemia. J Am Soc Nephrol 19:1311–1320

    Article  PubMed  CAS  Google Scholar 

  • Matute-Bello G, Frevert CW, Martin TR (2008) Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295:L379–L399

    Article  PubMed  CAS  Google Scholar 

  • McCampbell A, Taye AA, Whitty L et al (2001) Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc Natl Acad Sci USA 98:15179–15184

    Article  PubMed  CAS  Google Scholar 

  • Meriin AB, Yaglom JA, Gabai VL et al (1999) Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72. Mol Cell Biol 19(4):2547–2555

    PubMed  CAS  Google Scholar 

  • Mollen KP, Levy RM, Prince JM et al (2008) Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells. J Leukoc Biol 83(1):80–88

    Article  PubMed  CAS  Google Scholar 

  • Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65(21):9603–9606

    Article  PubMed  CAS  Google Scholar 

  • Mosser DD, Caron AW, Bourget L et al (2000) The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20(19):7146–7159

    Article  PubMed  CAS  Google Scholar 

  • Moochhala S, Wu J, Lu J (2009) Hemorrhagic shock: an overview of animal models. Front Biosci 14:4631

    Article  PubMed  CAS  Google Scholar 

  • Murphy TJ, Paterson HM, Mannick JA, Lederer JA (2004) Injury, sepsis, and the regulation of toll-like receptor responses. J Leukoc Biol 75(3):400–407

    Article  PubMed  CAS  Google Scholar 

  • Okumura K, Mendoza M, Bachoo RM et al (2006) PCAF modulates PTEN activity. J Biol Chem 281:26562–26568

    Article  PubMed  CAS  Google Scholar 

  • Oudit GY, Sun H, Kerfant BG, Crackower MA, Penninger JM, Backx PH (2004) The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease. J Mol Cell Cardiol 37:449–471

    Article  PubMed  CAS  Google Scholar 

  • Overhaus M, Toegel S, Bauer AJ (2009) Interaction of hemorrhagic shock and subsequent polymicrobial sepsis on gastrointestinal motility. Shock 31(4):382–389

    Article  PubMed  Google Scholar 

  • Park HS, Cho SG, Kim CK et al (2002) Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol 22(22):7721–7730

    Article  PubMed  CAS  Google Scholar 

  • Peitzman AB, Billiar TR, Harbrecht BG et al (1995) Hemorrhagic shock. Curr Probl Surg 32(11):925–1002

    Article  PubMed  CAS  Google Scholar 

  • Perkins ND (2007) Integrating cell-signaling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8(1):49–62

    Article  PubMed  CAS  Google Scholar 

  • Petri S, Kiaei M, Kipiani K et al (2006) Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 22:40–49

    Article  PubMed  CAS  Google Scholar 

  • Petri B, Phillipson M, Kubes P (2008) The physiology of leukocyte recruitment: an in vivo perspective. J Immunol 180:6439–6446

    PubMed  CAS  Google Scholar 

  • Ping P, Murphy E (2000) Role of p38 mitogen-activated protein kinases in preconditioning: a detrimental factor or a protective kinase? Circ Res 86(9):989–997

    Google Scholar 

  • Quivy V, Adam E, Collette Y et al (2002) Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappaB and inhibitors of deacetylases: potential perspectives for the development of therapeutic strategies. J Virol 76(21):11091–11103

    Article  PubMed  CAS  Google Scholar 

  • Rana MW, Singh G, Wang P et al (1992) Protective effects of preheparinization on the microvasculature during and after hemorrhagic shock. J Trauma 32:420–426

    Article  PubMed  CAS  Google Scholar 

  • Roger TH, Babensee JE (2010) Altered adherent leukocyte profile on biomaterials in toll-like receptor 4 deficient mice. Biomaterials 31(4):594–601

    Article  CAS  Google Scholar 

  • Ryu H, Lee J, Plpfsson BA et al (2003) Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via a Sp1-dependent pathway. Proc Nalt Acad Sci USA 100(7):4281–4286

    Article  CAS  Google Scholar 

  • Ryu H, Smith K, Camelo SI et al (2005) Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis. J Neurochem 93:1087–1098

    Article  PubMed  CAS  Google Scholar 

  • Saccani S, Pantano S, Natoli G (2002) p38-depedent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol 3(1):69–75

    Article  PubMed  CAS  Google Scholar 

  • Saha RN, Pahan K (2006) HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ 13:539–550

    Article  PubMed  CAS  Google Scholar 

  • Sailhamer ES, Li Y, Smith EJ et al (2008) Acetylation: a novel method for modulation of the immune response following trauma/hemorrhage and inflammatory second hit in animals and humans. Surgery 144(2):204–216

    Article  PubMed  Google Scholar 

  • Saitoh M, Nishitoh H, Fujii M et al (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17:2596–26026

    Article  PubMed  CAS  Google Scholar 

  • Saleh A, Srinivasula SM, Balkir L et al (2000) Negative regulation of the Apaf-1 apoptosome by Hsp70. Nat Cell Biol 2:476–483

    Article  PubMed  CAS  Google Scholar 

  • Saltiel AR (2003) Putting the brakes on insulin signaling. N Engl J Med 349(26):2560–2562

    Article  PubMed  CAS  Google Scholar 

  • Schwartzbauer G, Robbins J (2001) The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival. J Biol Chem 276:35786–35793

    Article  PubMed  CAS  Google Scholar 

  • Scher MB, Vaquero A, Reinberg D (2007) SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 21(8):920–928

    Article  PubMed  CAS  Google Scholar 

  • Shih HC, Wei YH, Lee CH (2003) Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats. Shock 20(3):264–268

    Article  PubMed  CAS  Google Scholar 

  • Shuja F, Tabbara M, Li Y, Liu B, Butt MU, Velmahos GC, deMoya M, Alam H (2009) Profound hypothermia decreases cardiac apoptosis through Akt survival pathway. J Am Coll Surg 209:89–99

    Article  PubMed  Google Scholar 

  • Shults C, Sailhamer EA, Li Y, Liu B, Tabbara M, Butt MU, Shuja F, Demoya M, Velmahos G, Alam HB (2008) Surviving blood loss without fluid resuscitation. J Trauma 64(3):629–638

    Article  PubMed  Google Scholar 

  • Stambolic V, Suzuki A, de la Pompa JL et al (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39

    Article  PubMed  CAS  Google Scholar 

  • Stankiewicz AR, Lachapelle G, Foo CP et al (2005) Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem 280(46):38729–38739

    Article  PubMed  CAS  Google Scholar 

  • Steffan JS, Bodai L, Pallos J et al (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413:739–743

    Article  PubMed  CAS  Google Scholar 

  • Stiles B, Groszer M, Wang S et al (2004) PTENless means more. Dev Biol 273:175–184

    Article  PubMed  CAS  Google Scholar 

  • St-pierre J, Drori S, Uldry M et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127(2):397–408

    Article  PubMed  CAS  Google Scholar 

  • Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19(5):233–238

    Article  PubMed  CAS  Google Scholar 

  • Suuronen T, Ojala J, Hyttinen JM et al (2008) Regulation of ER alpha signaling pathway in neuronal HN10 cells: role of protein acetylation and Hsp90. Neurochem Res 33(9):1768–1775

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T (2009) Explorative study on isoform-selective histone deacetylase inhibitors. Chem Pharm Bull 57(9):897–906

    Article  Google Scholar 

  • Tamguney T, Strokoe D (2007) New insight into PTEN. J Cell Sci 120(Pt23):4071–4079

    Article  PubMed  CAS  Google Scholar 

  • Thomson S, Clayton AL, Hazzalin CA et al (1999) The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 18(17):4779–4793

    Article  PubMed  CAS  Google Scholar 

  • Thuijls G, de Haan JJ, Derikx JP et al (2009) Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock. Shock 31:164–169

    Article  PubMed  CAS  Google Scholar 

  • Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I et al (2004) Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 94:514–524

    Article  PubMed  CAS  Google Scholar 

  • Tsan MF, Gao B (2009) Heat shock proteins and immune system. J Leukoc Biol 85(6):905–910

    Article  PubMed  CAS  Google Scholar 

  • Ungerstedt JS, Sowa Y, Xu WS et al (2005) Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Pro Natl Acad Sci USA 102(3):673–678

    Article  CAS  Google Scholar 

  • Vadlamani L, Lyengar S (2004) Tumor necrosis factor alpha polymorphism in heart failure/cardiomyopathy. Congest Heart Fail 10(6):289–292

    Article  PubMed  CAS  Google Scholar 

  • Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84

    Article  PubMed  CAS  Google Scholar 

  • Vanden Berghe W, De Bosscher K, Boone E et al (1999) The nuclear factor-kappaB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter. J Biol Chem 274(45):32091–32098

    Article  Google Scholar 

  • Vidali G, Gershey E, Allfrey VG (1968) Chemical studies of histone acetylation. The distribution of ε-N-acetyllysine in calf thymus histones. J Biol Chem 243:6361–6366

    PubMed  CAS  Google Scholar 

  • Voelter-Mahlknecht S, Ho AD, Mahlknecht U (2005) Chromasomal organization and localization of novel class IV human histone deacetylase 11 gene. Int J Mol Med 16(4):589–598

    PubMed  CAS  Google Scholar 

  • Volloch V, Gabai VL, Rits S et al (1999) ATPase activity of the heat shock protein hsp72 is dispensable for its effects on dephosphorylation of stress kinase JNK and on heat-induced apoptosis. FEBS Lett 461(1–2):73–76

    Article  PubMed  CAS  Google Scholar 

  • Weichert W (2009) HDAC expression and clinical prognosis in human malignancies. Cancer Lett 280(2):168–176

    Article  PubMed  CAS  Google Scholar 

  • Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376

    Article  PubMed  CAS  Google Scholar 

  • Winter-Vann AM, Johnson GL (2007) Integrated activation of MAP3Ks balances cell fate in response to stress. J Cell Biochem 102(4):848–858

    Article  PubMed  CAS  Google Scholar 

  • Wong V, Gumbiner BM (1997) A synthetic peptide corresponding to the extracellular domain of occluding perturbs the tight junction permeability barrier. J Cell Biol 136:399–409

    Article  PubMed  CAS  Google Scholar 

  • Xu YX, Ayala A, Chaudry IH (1998) Prolonged immunodepression after trauma and hemorrhagic shock. J Trauma 44:335–341

    Article  PubMed  CAS  Google Scholar 

  • Yao XH, Nyomba BL (2008) Hepatic resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring. Am J Physiol Regul Integr Comp Physiol 294(6):R1797–R1806

    Article  PubMed  CAS  Google Scholar 

  • Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151

    PubMed  CAS  Google Scholar 

  • Yildirim F, Gertz K, Kronenberg G et al (2008) Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury. Exp Neurol 210(2):531–542

    Article  PubMed  CAS  Google Scholar 

  • Zacharias N, Sailhamer EA, Li Y, Liu B, Butt MU, Shuja F, Velmahos GC, de Moya M, Alam HB et al (2010) Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells. Resuscitation, 29 October 2010 [Epub ahead of print]

    Google Scholar 

  • Zarbock A, Ley K (2009) Neutrophil adhesion and activation under flow. Microcirculation 16:31–42

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Wan J, Jiang R et al (2009) Protective effects of trichostatin A on liver injury in septic mice. Hepatol Res 39:931–938

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Jin S, Wang C et al (2010) Histone deacetylase inhibitors attenuate acute lung injury during cecal ligation and puncture-induced polymicrobial sepsis. World J Surg 34(7):1676–1683

    Article  PubMed  Google Scholar 

  • Zhao TC, Cheng G, Zhang LX et al (2007) Inhibition of histone deacetylases triggers pharmacologic preconditioning effects against myocardial ischemic injury. Cardiovasc Res 76(3):473–481

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Dr. Alam acknowledges grant support from the National Institutes of Health (RO1 GM084127), Defense Advanced Research Projects Agency (W911NF-06-1-0220), Office of Naval Research (N000140910378), and the US Army Medical Research Material Command (GRANTT00521959).

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Authors and Affiliations

  1. Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

    Yongqing Li

  2. Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, 165 Cambridge Street, Suite 810, Boston, MA, 02114, USA

    Hasan B. Alam

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  1. Yongqing Li
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  2. Hasan B. Alam
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Correspondence to Hasan B. Alam .

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  1. Massachusetts General Hospital, Harvard Medical School, Fruit Street 55, Boston, 02114-2696, Massachusetts, USA

    Eleftherios Mylonakis

  2. Massachusetts General Hospital, Harvard Medical School, Cambridge Street 185, Boston, 02114, Massachusetts, USA

    Frederick M. Ausubel

  3. Schepens Eye Research Inst., Harvard Medical School, Staniford St. 20, Boston, 02114, Massachusetts, USA

    Michael Gilmore

  4. Albert Einstein College of Medicine, Dept. Microbiology & Immunology, Yeshiva University, Morris Park Ave. 1300, Bronx, 10461, New York, USA

    Arturo Casadevall

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Li, Y., Alam, H.B. (2012). Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock. In: Mylonakis, E., Ausubel, F., Gilmore, M., Casadevall, A. (eds) Recent Advances on Model Hosts. Advances in Experimental Medicine and Biology, vol 710. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5638-5_11

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