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The role of redox modulation of class II histone deacetylases in mediating pathological cardiac hypertrophy

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Abstract

Many biological functions in cells are regulated by the effects of the redox state on cellular signaling pathways. In the heart, pathological hypertrophy caused by a wide variety of stimuli is commonly mediated by nucleo-cytoplasmic translocation of class II histone deacetylases (HDACs) and subsequent de-suppression of transcription factors, including nuclear factor of activated T-cells and MEF2. One of the primary triggers of class II HDAC nuclear export is phosphorylation by HDAC kinases activated by hypertrophic stimuli. However, oxidative modification of conserved cysteine residues can also potentially induce nuclear export of class II HDACs. Thioredoxin 1 (Trx1), a 12 kDa anti-oxidant, inhibits pathological hypertrophy through reduction of cysteine residues in class II HDACs. In this review, we discuss the role of posttranslational modification of class II HDACs in mediating cardiac hypertrophy and the molecular mechanism by which Trx1 inhibits pathological cardiac hypertrophy.

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References

  1. Sadoshima J (2006) Redox regulation of growth and death in cardiac myocytes. Antioxid Redox Signal 8:1621–1624

    Article  PubMed  CAS  Google Scholar 

  2. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, Zhang XQ, Stevenson TJ, Peshock RM, Leopold JA, Barry WH, Loscalzo J, Odelberg SJ, Benjamin IJ (2007) Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:427–439

    Article  PubMed  CAS  Google Scholar 

  3. Masutani H, Yodoi J (2002) Thioredoxin. Overview. Methods Enzymol 347:279–286

    Article  PubMed  CAS  Google Scholar 

  4. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    Article  PubMed  CAS  Google Scholar 

  5. Khochbin S, Verdel A, Lemercier C, Seigneurin-Berny D (2001) Functional significance of histone deacetylase diversity. Curr Opin Genet Dev 11:162–166

    Article  PubMed  CAS  Google Scholar 

  6. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749

    Article  PubMed  Google Scholar 

  7. Masoro EJ (2004) Role of sirtuin proteins in life extension by caloric restriction. Mech Ageing Dev 125:591–594

    Article  PubMed  CAS  Google Scholar 

  8. Backs J, Olson EN (2006) Control of cardiac growth by histone acetylation/deacetylation. Circ Res 98:15–24

    Article  PubMed  CAS  Google Scholar 

  9. Song K, Backs J, McAnally J, Qi X, Gerard RD, Richardson JA, Hill JA, Bassel-Duby R, Olson EN (2006) The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases. Cell 125:453–466

    Article  PubMed  CAS  Google Scholar 

  10. Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin JD, Vatner SF, Sadoshima J (2008) A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell 133:978–993

    Article  PubMed  CAS  Google Scholar 

  11. Berk BC (1999) Angiotensin II signal transduction in vascular smooth muscle: pathways activated by specific tyrosine kinases. J Am Soc Nephrol 10:S62–S68

    PubMed  CAS  Google Scholar 

  12. Wu X, Zhang T, Bossuyt J, Li X, McKinsey TA, Dedman JR, Olson EN, Chen J, Brown JH, Bers DM (2006) Local InsP3-dependent perinuclear Ca2 + signaling in cardiac myocyte excitation-transcription coupling. J Clin Invest 116:675–682

    Article  PubMed  CAS  Google Scholar 

  13. Zhang T, Kohlhaas M, Backs J, Mishra S, Phillips W, Dybkova N, Chang S, Ling H, Bers DM, Maier LS, Olson EN, Brown JH (2007) CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses. J Biol Chem 282:35078–35087

    Article  PubMed  CAS  Google Scholar 

  14. Backs J, Backs T, Neef S, Kreusser MM, Lehmann LH, Patrick DM, Grueter CE, Qi X, Richardson JA, Hill JA, Katus HA, Bassel-Duby R, Maier LS, Olson EN (2009) The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci USA 106:2342–2347

    Article  PubMed  CAS  Google Scholar 

  15. Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (2004) Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5. Mol Cell Biol 24:8374–8385

    Article  PubMed  CAS  Google Scholar 

  16. Martini JS, Raake P, Vinge LE, DeGeorge B Jr, Chuprun JK, Harris DM, Gao E, Eckhart AD, Pitcher JA, Koch WJ (2008) Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc Natl Acad Sci USA 105:12457–12462

    Article  PubMed  CAS  Google Scholar 

  17. Berdeaux R, Goebel N, Banaszynski L, Takemori H, Wandless T, Shelton GD, Montminy M (2007) SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med 13:597–603

    Article  PubMed  CAS  Google Scholar 

  18. Chang S, Bezprozvannaya S, Li S, Olson EN (2005) An expression screen reveals modulators of class II histone deacetylase phosphorylation. Proc Natl Acad Sci USA 102:8120–8125

    Article  PubMed  CAS  Google Scholar 

  19. Sorescu D, Griendling KK (2002) Reactive oxygen species, mitochondria, and NAD(P) H oxidases in the development and progression of heart failure. Congest Heart Fail 8:132–140

    Article  PubMed  CAS  Google Scholar 

  20. Zhang M, Shah AM (2007) Role of reactive oxygen species in myocardial remodeling. Curr Heart Fail Rep 4:26–30

    Article  PubMed  CAS  Google Scholar 

  21. El Benna J, Faust RP, Johnson JL, Babior BM (1996) Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J Biol Chem 271:6374–6378

    Article  PubMed  CAS  Google Scholar 

  22. Aikawa R, Nagai T, Tanaka M, Zou Y, Ishihara T, Takano H, Hasegawa H, Akazawa H, Mizukami M, Nagai R, Komuro I (2001) Reactive oxygen species in mechanical stress-induced cardiac hypertrophy. Biochem Biophys Res Commun 289:901–907

    Article  PubMed  CAS  Google Scholar 

  23. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88:529–535

    PubMed  CAS  Google Scholar 

  24. Marin-Garcia J, Pi Y, Goldenthal MJ (2006) Mitochondrial-nuclear cross-talk in the aging and failing heart. Cardiovasc Drugs Ther 20:477–491

    Article  PubMed  CAS  Google Scholar 

  25. Ekelund UE, Harrison RW, Shokek O, Thakkar RN, Tunin RS, Senzaki H, Kass DA, Marban E, Hare JM (1999) Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure. Circ Res 85:437–445

    PubMed  CAS  Google Scholar 

  26. Murtaza I, Wang HX, Feng X, Alenina N, Bader M, Prabhakar BS, Li PF, Jacob MH, Pontes MR, Araujo AS, Barp J, Irigoyen MC, Llesuy SF, Ribeiro MF, Bello-Klein A (2008) Down-regulation of catalase and oxidative modification of protein kinase CK2 lead to the failure of apoptosis repressor with caspase recruitment domain to inhibit cardiomyocyte hypertrophy. J Biol Chem 283:5996–6004

    Article  PubMed  CAS  Google Scholar 

  27. Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG, Prabhu SD (2007) Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res 74:445–455

    Article  PubMed  CAS  Google Scholar 

  28. Xu D, Rovira II, Finkel T (2002) Oxidants painting the cysteine chapel: redox regulation of PTPs. Dev Cell 2:251–252

    Article  PubMed  CAS  Google Scholar 

  29. Tonks NK (2005) Redox redux: revisiting PTPs and the control of cell signaling. Cell 121:667–670

    Article  PubMed  CAS  Google Scholar 

  30. Tabet F, Schiffrin EL, Callera GE, He Y, Yao G, Ostman A, Kappert K, Tonks NK, Touyz RM (2008) Redox-sensitive signaling by angiotensin II involves oxidative inactivation and blunted phosphorylation of protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells from SHR. Circ Res 103:149–158

    Article  PubMed  CAS  Google Scholar 

  31. Storz P, Doppler H, Toker A (2005) Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Mol Cell Biol 25:8520–8530

    Article  PubMed  CAS  Google Scholar 

  32. Banday AA, Lokhandwala MF (2008) Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension. Am J Physiol Renal Physiol 295:F698–F706

    Article  PubMed  CAS  Google Scholar 

  33. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O'Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133:462–474

    Article  PubMed  CAS  Google Scholar 

  34. Bottomley MJ, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, De Francesco R, Steinkuhler C, Gallinari P, Carfi A (2008) Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain. J Biol Chem 283:26694–26704

    Article  PubMed  CAS  Google Scholar 

  35. Nott A, Watson PM, Robinson JD, Crepaldi L, Riccio A (2008) S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons. Nature 455:411–415

    Article  PubMed  CAS  Google Scholar 

  36. Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ, Epstein JA (2007) Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med 13:324–331

    Article  PubMed  CAS  Google Scholar 

  37. Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H, Takagi Y, Sono H, Gon Y, Yodoi J (1999) Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression. J Biol Chem 274:21645–21650

    Article  PubMed  CAS  Google Scholar 

  38. Oka S, Masutani H, Liu W, Horita H, Wang D, Kizaka-Kondoh S, Yodoi J (2006) Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR) gamma ligand target protein that regulates PPARgamma signaling. Endocrinology 147:733–743

    Article  PubMed  CAS  Google Scholar 

  39. Hui ST, Andres AM, Miller AK, Spann NJ, Potter DW, Post NM, Chen AZ, Sachithanantham S, Jung DY, Kim JK, Davis RA (2008) Txnip balances metabolic and growth signaling via PTEN disulfide reduction. Proc Natl Acad Sci USA 105:3921–3926

    Article  PubMed  CAS  Google Scholar 

  40. Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA, Richon VM (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 99:11700–11705

    Article  PubMed  CAS  Google Scholar 

  41. Qiu XB, Shao YM, Miao S, Wang L (2006) The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63:2560–2570

    Article  PubMed  CAS  Google Scholar 

  42. Dai YS, Xu J, Molkentin JD (2005) The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol 25:9936–9948

    Article  PubMed  CAS  Google Scholar 

  43. Kee HJ, Eom GH, Joung H, Shin S, Kim JR, Cho YK, Choe N, Sim BW, Jo D, Jeong MH, Kim KK, Seo JS, Kook H (2008) Activation of histone deacetylase 2 by inducible heat shock protein 70 in cardiac hypertrophy. Circ Res 103:1259–1269

    Article  PubMed  CAS  Google Scholar 

  44. Choi HI, Lee SP, Kim KS, Hwang CY, Lee YR, Chae SK, Kim YS, Chae HZ, Kwon KS (2006) Redox-regulated cochaperone activity of the human DnaJ homolog Hdj2. Free Radic Biol Med 40:651–659

    Article  PubMed  CAS  Google Scholar 

  45. Nishinaka Y, Masutani H, Oka S, Matsuo Y, Yamaguchi Y, Nishio K, Ishii Y, Yodoi J (2004) Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2/vitamin D(3)-up-regulated protein 1. J Biol Chem 279:37559–37565

    Article  PubMed  CAS  Google Scholar 

  46. Ago T, Sadoshima J (2007) Thioredoxin1 as a negative regulator of cardiac hypertrophy. Antioxid Redox Signal 9:679–687

    Article  PubMed  CAS  Google Scholar 

  47. Haendeler J, Hoffmann J, Tischler V, Berk BC, Zeiher AM, Dimmeler S (2002) Redox regulatory and anti-apoptotic functions of thioredoxin depend on S-nitrosylation at cysteine 69. Nat Cell Biol 4:743–749

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was in part supported by US Public Health Service Grants HL 59139, HL67724, HL67727, HL69020, and HL 73048.

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Authors and Affiliations

  1. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 S Orange Ave., MSB G609, Newark, NJ, 07103, USA

    Shin-ichi Oka, Daniela Zablocki & Junichi Sadoshima

  2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Tetsuro Ago & Takanari Kitazono

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  1. Shin-ichi Oka
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  2. Tetsuro Ago
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Correspondence to Junichi Sadoshima.

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Oka, Si., Ago, T., Kitazono, T. et al. The role of redox modulation of class II histone deacetylases in mediating pathological cardiac hypertrophy. J Mol Med 87, 785–791 (2009). https://doi.org/10.1007/s00109-009-0471-2

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