Advertisement

Apoptosis

, Volume 21, Issue 7, pp 763–777 | Cite as

Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12

  • Selene García de la Cadena
  • Lourdes Massieu
Review

Abstract

Caspases are cysteine proteases, which play important roles in different processes including, apoptosis and inflammation. Caspase-12, expressed in mouse and human, is classified as an inflammatory caspase. However, in humans caspase-12 gene has acquired different mutations that result in the expression of different variants. Caspase-12 is generally recognized as a negative regulator of the inflammatory response induced by infections, because it inhibits the activation of caspase-1 in inflammasome complexes, the production of the pro-inflammatory cytokines IL-1β and IL-18 and the overall response to sepsis. In contrast, caspase-4, the human paralog of caspase-12, exerts a positive modulatory action of the inflammatory response to infectious agents. The role of caspase-12 and caspase-4 in inflammation associated with cerebral ischemia, a condition that results from a transient or permanent reduction of cerebral blood flow, is still unknown. Among the mechanisms involved in ischemic brain injury, apoptosis and inflammation have important roles. Under these conditions, disturbances in the homeostasis of the endoplasmic reticulum (ER) take place, leading to ER stress, caspase activation and apoptosis. Caspase-12 up-regulation and processing has been observed after the ischemic episode but its role in apoptosis is controversial. Cleavage of caspase-4 also occurs during ER stress but its role in ischemic brain injury is unknown. Throughout this review evidence supporting a role of caspase-12 and caspase-4 on the modulation of the inflammatory response to infection and their potential contribution to ER stress-induced apoptosis, is discussed. Understanding the actions of rodent caspase-12 and human caspase-4 will help us to elucidate their role in different pathological conditions, which to date is not well understood.

Keywords

Caspases Apoptosis Inflammation Cerebral ischemia ER stress Caspase-4 Caspase-12 

Abbreviations

CARD

Caspase-recruitment domain

DED

Death effector domain

DD

Death domain

DISC

Death inducing signaling complex

NLR

NOD-like receptor

ALR

AIM2 (absent in melanoma 2)-like receptor

ER

Endoplasmic reticulum

IRE1

Inositol-requiring enzyme 1

ATF6

Activating transcription factor 6

PERK

Protein kinase RNA (PKR)-like ER kinase

GRP78

78-kDa glucose-regulated protein

eIF2α

α-Subunit of the eukaryotic translation initiation factor-2

ATF4

Activating transcription factor 4

XBP1

X-Box-binding protein 1

CHOP

C/EBP homologous protein

MCAO

Middle cerebral artery occlusion

OGD

Oxygen–glucose deprivation

Notes

Acknowledgments

We apologize to all authors whose work could not be cited in the present review due to space limitations. LM laboratory work has been supported by CB239607 CONACYT and IN204213 PAPIIT (UNAM) Grants and S.G.C. was supported by 221026 CONACYT.

References

  1. 1.
    Parrish AB, Freel CD, Kornbluth S (2013) Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol 5:1–24CrossRefGoogle Scholar
  2. 2.
    Chowdhury I, Tharakan B, Bhat GK (2008) Caspases—an update. Comp Biochem Physiol B 151:10–27PubMedCrossRefGoogle Scholar
  3. 3.
    Shalini S, Dorstyn L, Dawar S, Kumar S (2014) Old, new and emerging functions of caspases. Cell Death Differ 21:1–14CrossRefGoogle Scholar
  4. 4.
    Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasomes. Cell 157:1013–1022PubMedCrossRefGoogle Scholar
  5. 5.
    Park HH (2012) Structural features of caspase-activating complexes. Int J Mol Sci 13:4807–4818PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMedCrossRefGoogle Scholar
  7. 7.
    Mcllwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 5:1–28Google Scholar
  8. 8.
    Creagh EM (2014) Caspase crosstalk: integration of apoptotic and innate immune signalling pathways. Trends Immunol 35:631–640PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326:1–16PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wang ZB, Liu YQ, Cui YF (2005) Pathways to caspase activation. Cell Biol Int 29:489–496PubMedCrossRefGoogle Scholar
  11. 11.
    Hermel E, Klapstein K (2011) A possible mechanism for maintenance of the deleterious allele of human caspase-12. Med Hypotheses 77:803–806PubMedCrossRefGoogle Scholar
  12. 12.
    Denault JB, Salvesen GS (2002) Caspases: keys in the ignition of cell death. Chem Rev 102:4489–4499PubMedCrossRefGoogle Scholar
  13. 13.
    Park HH, Wu H (2006) Crystal structure of RAIDD death domain implicates potential mechanism of PIDDosome assembly. J Mol Biol 357:358–364PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Kersse T, Vanden Berghe T, Lamkanfi M, Vandenabeele P (2007) A phylogenetic and functional overview of inflammatory caspases and caspase-1-related CARD-only proteins. Biochem Soc Trans 35:1508–1511PubMedCrossRefGoogle Scholar
  15. 15.
    Sollberger G, Strittmatter GE, Kistowska M, French LE, Beer HD (2012) Caspase-4 is required for activation of inflammasomes. J Immunol 188:1992–2000PubMedCrossRefGoogle Scholar
  16. 16.
    Kersse K, Vandenabeele P (2013) Caspase-12. In: Rawlings ND, Salvesen GS (eds) Handbook of proteolytic enzymes, 3rd edn. Academic Press, Oxford, pp 2274–2280CrossRefGoogle Scholar
  17. 17.
    Jiménez D, Lamkanfi M (2015) Inflammatory caspases: key regulators of inflammation and cell death. Biol Chem 396:193–203Google Scholar
  18. 18.
    Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832PubMedCrossRefGoogle Scholar
  19. 19.
    Chavarría-Smith J, Vance R (2014) The NLRP1 inflammasomes. Immunol Rev 265:22–34CrossRefGoogle Scholar
  20. 20.
    Casson CN, Copenhaver AM, Zwack EE, Nguyen HT, Strowig T, Javdan B, Bradley WP, Fung TC, Flavell RA, Brodsky IE, Shin S (2013) Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLoS Pathog 9:1–16CrossRefGoogle Scholar
  21. 21.
    Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszynski A, Forsberg LS, Carlson RW, Dixit VM (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341:1246–1249PubMedCrossRefGoogle Scholar
  22. 22.
    Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F (2014) Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514:187–192PubMedCrossRefGoogle Scholar
  23. 23.
    Casson CN, Yu J, Reyes VM, Taschuk FO, Yadav A, Copenhaver AM, Nguyen HT, Collman RG, Shin S (2015) Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens. Proc Natl Acad Sci USA 112:6688–6693PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Knodler LA, Crowley SM, Sham HP, Yang H, Wrande M, Ma C, Ernst RK, Steele-Mortimer O, Celli J, Vallance BA (2014) Non-canonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 16:249–256PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Baker PJ, Boucher D, Bierschenk D, Tebartz C, Whitney PG, D’Silva DB, Tanzer MC, Monteleone M, Robertson AA, Cooper MA, Alvarez-Diaz S, Herold MJ, Bedoui S, Schroder K, Masters SL (2015) NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur J Immunol 45:2918–2926PubMedCrossRefGoogle Scholar
  26. 26.
    Schmid-Burgk JL, Gaidt MM, Schmidt T, Ebert TS, Bartok E, Hornung V (2015) Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. Eur J Immunol 45:2911–2917PubMedCrossRefGoogle Scholar
  27. 27.
    Kajiwara Y, Schiff T, Voloudakis G, Gama Sosa MA, Elder G, Bozdagi O, Buxbaum JD (2014) A critical role for human caspase-4 in endotoxin sensitivity. J Immunol 193:335–343PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Lakshmanan U, Porter AG (2007) Caspase-4 interacts with TNF receptor-associated factor 6 and mediates lipopolysaccharide-induced NF-κB-dependent production of IL-8 and CC chemokine ligand 4 (macrophage-inflammatory protein-1β). J Immunol 179:8480–8490PubMedCrossRefGoogle Scholar
  29. 29.
    Sanders MG, Parsons MJ, Howard AG, Liu J, Fassio SR, Martinez JA, Bouchier-Hayes L (2015) Single-cell imaging of inflammatory caspase dimerization reveals differential recruitment to inflammasomes. Cell Death Dis 6:1–11CrossRefGoogle Scholar
  30. 30.
    Gringhuis S, Kaptein TM, Wevers BA, Theelen B, Van der Vlist M, Boekhout T, Geijtenbeek TBH (2012) Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome. Nat Immunol 13:246–255PubMedCrossRefGoogle Scholar
  31. 31.
    Philip NH, Dillon CP, Snyder AG, Fitzgerald P, Wynosky-Dolfi MA, Zwack EE, Hu B, Fitzgerald L, Mauldin EA, Copenhaver AM, Shin S, Wei L, Parker M, Zhang J, Oberst A, Green DR, Brodsky IE (2014) Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling. Proc Natl Acad Sci USA 111:7385–7390PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gurung P, Anand PK, Malireddi RK, Vande Walle L, Van Opdenbosch N, Dillon CP, Weinlich R, Green DR, Lamkanfi M, Kanneganti TD (2014) FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J Immunol 192:1835–1846PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Fann DYW, Lee SY, Manzanero S, Chunduri P, Sobey C, Arumugam T (2013) Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev 12:941–966PubMedCrossRefGoogle Scholar
  34. 34.
    Hotchkiss RS, Nicholson DW (2006) Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 6:813–822PubMedCrossRefGoogle Scholar
  35. 35.
    Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signaling. Nature 526:666–671PubMedCrossRefGoogle Scholar
  36. 36.
    Nadiri A, Wolinski MK, Saleh M (2006) The inflammatory caspases: key players in the host response to pathogenic invasion and sepsis. J Immunol 77:4239–4245CrossRefGoogle Scholar
  37. 37.
    Martinon F, Tschopp J (2007) Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ 14:10–22PubMedCrossRefGoogle Scholar
  38. 38.
    Scott AM, Saleh M (2007) The inflammatory caspases: guardians against infections and sepsis. Cell Death Differ 14:23–31PubMedCrossRefGoogle Scholar
  39. 39.
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase-12 mediates endoplasmic reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403:98–103PubMedCrossRefGoogle Scholar
  40. 40.
    Kalai M, Lamkanfi M, Denecker G, Boogmans M, Lippens S, Meeus A, Declercq W, Vandenabeele P (2003) Regulation of the expression and processing of caspase-12. J Cell Biol 162:457–467PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Kachapati K, O’brien TR, Bergeron J, Zhang M, Dean M (2006) Population distribution of the functional caspase-12 allele. Hum Mutat 27:975–980PubMedCrossRefGoogle Scholar
  42. 42.
    Fischer H, Koenig U, Eckhart L, Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 293:722–726PubMedCrossRefGoogle Scholar
  43. 43.
    Saleh M, Mathison JC, Wolinski MK, Bensinger SJ, Fitzgerald P, Droin N, Ulevitch RJ, Green DR, Nicholson DW (2006) Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440:1064–1068PubMedCrossRefGoogle Scholar
  44. 44.
    Xue Y, Daly A, Yngvadottir B, Liu M, Coop G, Kim Y, Sabeti P, Chen Y, Stalker J, Huckle E, Burton J, Leonard S, Rogers J, Tyler-Smith C (2006) Spread of an inactive form of caspase-12 in humans is due to recent positive selection. Am J Hum Genet 78:659–670PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholson DW (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429:75–79PubMedCrossRefGoogle Scholar
  46. 46.
    Rosentul D, Plantinga T, Scott W, Alexander B, Van de Geer N, Perfect J, Kullberg B, Johnson M, Netea M (2012) The impact of caspase-12 on susceptibility to candidemia. Eur J Clin Microbiol Infect Dis 31:277–280PubMedCrossRefGoogle Scholar
  47. 47.
    Roy S, Sharom JR, Houde C, Loisel TP, Vaillancourt JP, Shao W, Saleh M, Nicholson DW (2008) Confinement of caspase-12 proteolytic activity to autoprocessing. Proc Natl Acad Sci USA 105:4133–4138PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    LeBlanc PM, Yeretssian G, Rutherford N, Doiron K, Nadiri A, Zhu L, Green DR, Gruenheid S, Saleh M (2008) Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity. Cell Host Microbe 3:146–157PubMedCrossRefGoogle Scholar
  49. 49.
    Labbé K, Miu J, Yeretssian G, Serghides L, Tam M, Finney C, Erdman L, Goulet ML, Kain K, Stevenson M, Saleh M (2010) Caspase-12 dampens the immune response to malaria independently of the inflammasome by targeting NF-κB signaling. J Immunol 185:5495–5502PubMedCrossRefGoogle Scholar
  50. 50.
    Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM (2011) Non-canonical inflammasome activation targets caspase-11. Nature 479:117–121PubMedCrossRefGoogle Scholar
  51. 51.
    Galluzzi López-Soto A, Kumar S, Kroemer G (2016) Caspases connect cell-death signaling to organismal homeostasis. Immunity 44:221–231PubMedCrossRefGoogle Scholar
  52. 52.
    Wang P, Arjona A, Zhang Y, Sultana H, Dai J, Yang L, LeBlanc PM, Doiron K, Saleh M, Fikrig E (2010) Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nat Immunol 11:912–919PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Skeldon AM, Morizot A, Douglas T, Santoro N, Kursawe R, Kozlitina J, Caprio S, Mehal WZ, Saleh M (2016) Caspase-12, but not caspase-11, inhibits obesity and insulin resistance. J Immunol 196:437–447PubMedCrossRefGoogle Scholar
  54. 54.
    Trendelenburg G (2014) Molecular regulation of cell fate in cerebral ischemia: role of the inflammasome and connected pathways. J Cereb Blood Flow Metab 34:1857–1867PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Guo H, Callaway JB, Ting JP (2015) Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21:677–687PubMedCrossRefGoogle Scholar
  56. 56.
    Peng S, Kuang Z, Zhang Y, Xu H, Cheng Q (2011) The protective effects and potential mechanism of calpain inhibitor calpeptin against focal cerebral ischemia–reperfusion injury in rats. Mol Biol Rep 38:905–912PubMedCrossRefGoogle Scholar
  57. 57.
    Espinosa-García C, Vigueras-Villaseñor RM, Rojas-Castañeda JC, Aguilar-Hernández A, Monfil T, Cervantes M, Moralí G (2013) Post-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia. Neurosci Lett 550:98–103PubMedCrossRefGoogle Scholar
  58. 58.
    Wen XR, Fu YY, Liu HZ, Wu J, Shao XP, Zhang XB, Tang M, Shi Y, Ma K, Zhang F, Wang YW, Tang H, Han D, Zhang P, Wang SL, Xu Z, Song YJ (2015) Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting JNK3/Caspase-3 by enhancing Akt signaling pathway. Mol Neurobiol 51:1–11CrossRefGoogle Scholar
  59. 59.
    Benchoua A, Couriaud C, Guégan C, Tartier L, Couvert P, Friocourt G, Chelly J, Ménissier-de Murcia J, Onténiente B (2002) Active caspase-8 translocates into the nucleus of apoptotic cells to inactivate poly(ADP-ribose) polymerase-2. J Biol Chem 277:34217–34222PubMedCrossRefGoogle Scholar
  60. 60.
    Shabanzadeh AP, D’Onofrio PM, Monnier PP, Koeberle PD (2015) Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke. Cell Death Dis 6:1–13Google Scholar
  61. 61.
    Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397PubMedCrossRefGoogle Scholar
  62. 62.
    Leker RR, Shohami E (2002) Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities Brain. Res Rev 39:55–73CrossRefGoogle Scholar
  63. 63.
    Bramlett H, Dietrich WD (2004) Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J Cereb Blood Flow Metab 24:133–150PubMedCrossRefGoogle Scholar
  64. 64.
    Fann DYW, Lee SY, Manzanero S, Tang SC, Gelderblom M, Chunduri P, Bernreuther C, Glatzel M, Cheng YL, Thundyil J, Widiapradja A, Lok KZ, Foo SL, Wang YC, Li YI, Drummond GR, Basta M, Magnus T, Jo DG, Mattson MP, Sobey SG, Arumugam TV (2013) Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 4:1–10Google Scholar
  65. 65.
    Fann DYW, Santro T, Manzanero S, Widiapradja A, Cheng YL, Lee SY, Chunduri P, Jo DG, Stranahand AM, Mattson MP, Arumugam TV (2014) Intermittent fasting attenuates inflammasome activity in ischemic stroke. Exp Neurol 257:114–119PubMedCrossRefGoogle Scholar
  66. 66.
    Yang F, Wang Z, Wei X, Han H, Meng X, Zhang Y, Shi W, Li F, Xin T, Pang Q, Yi F (2014) NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab 34:660–667PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Zhang WH, Wang X, Narayanan M, Zhang Y, Huo C, Reed JC, Friedlander RM (2003) Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc Natl Acad Sci USA 100:16012–16017PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Mergenthaler P, Ulrich D, Meisel A (2004) Pathophysiology of stroke: lessons from animal models. Metab Brain Dis 19:151–167PubMedCrossRefGoogle Scholar
  69. 69.
    Schielke GP, Yang GY, Shivers BD, Betz AL (1998) Reduced ischemic brain injury in interleukin-lβ converting enzyme-deficient mice. J Cereb Blood Flow Metab 18:180–185PubMedCrossRefGoogle Scholar
  70. 70.
    Ross J, Brough D, Gibson RM, Loddick SA, Rothwell NJ (2007) A selective, non-peptide caspase-1 inhibitor, VRT-018858, markedly reduces brain damage induced by transient ischemia in the rat. Neuropharmacology 53:638–642PubMedCrossRefGoogle Scholar
  71. 71.
    Aoyama K, Burns DM, Suh SW, Garnier P, Matsumori Y, Shiina H, Swanson RA (2005) Acidosis causes endoplasmic reticulum stress and caspase-12-mediated astrocyte death. J Cereb Blood Flow Metab 25:358–370PubMedCrossRefGoogle Scholar
  72. 72.
    Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389PubMedCrossRefGoogle Scholar
  73. 73.
    Chen L, Gao X (2002) Neuronal apoptosis induced by endoplasmic reticulum stress. Neurochem Res 27:891–898PubMedCrossRefGoogle Scholar
  74. 74.
    Cao SS, Kaufman RJ (2012) Unfolded protein response. Curr Biol 22:622–626CrossRefGoogle Scholar
  75. 75.
    Schröder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29–63PubMedCrossRefGoogle Scholar
  76. 76.
    Wang S, Kaufman RJ (2012) The impact of the unfolded protein response on human disease. J Cell Biol 197:857–867PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinasa. Nature 397:271–274PubMedCrossRefGoogle Scholar
  78. 78.
    Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (2000) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 5:897–904PubMedCrossRefGoogle Scholar
  79. 79.
    Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM, Ron D (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 11:619–633PubMedCrossRefGoogle Scholar
  80. 80.
    Zinszner H, Kuroda M, Wang XZ, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12:982–995PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    McCullough KD, Martindale JL, Klotz L, Aw T, Holbrook NJ (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 21:1249–1259PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Reimertz C, Kögel D, Rami A, Chittenden T, Prehn JHM (2003) Gene expression during ER stress–induced apoptosis in neurons: induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway. J Cell Biol 162:587–597PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Logue SE, Cleary P, Saveljeva S, Samali A (2013) New directions in ER stress-induced cell death. Apoptosis 18:537–546PubMedCrossRefGoogle Scholar
  84. 84.
    Gardner BM, Pincus D, Gotthardt K, Gallagher CM, Walter P (2013) Endoplasmic reticulum stress sensing in the unfolded protein response. Cold Spring Harb Perspect Biol 5:1–15CrossRefGoogle Scholar
  85. 85.
    Ye J, Rawson RB, Komuro R, Chen X, Davé UP, Prywes R, Brown MS, Goldstein JL (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6:1355–1364PubMedCrossRefGoogle Scholar
  86. 86.
    Shen J, Prywes R (2005) ER stress signaling by regulated proteolysis of ATF6. Methods 35:382–389PubMedCrossRefGoogle Scholar
  87. 87.
    Chakrabarti A, Chen AW, Varner JD (2011) A review of the mammalian unfolded protein response. Biotechnol Bioeng 108:2777–2793PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Carrara M, Prischi F, Ali MU (2013) UPR signal activation by luminal sensor domains. Int J Mol Sci 14:6454–6466PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13:89–102PubMedGoogle Scholar
  90. 90.
    Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891PubMedCrossRefGoogle Scholar
  91. 91.
    Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92–96PubMedCrossRefGoogle Scholar
  92. 92.
    Lee K, Tirasophon W, Shen X (2002) IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 16:452–466PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Parmar VM, Schröder M (2012) Sensing endoplasmic reticulum stress. Adv Exp Med Biol 738:153–168PubMedCrossRefGoogle Scholar
  94. 94.
    Yk Oh, Shin KS, Yuan J, Kang SJ (2008) Superoxide dismutase 1 mutants related to amyotrophic lateral sclerosis induce endoplasmic stress in neuro2a cells. J Neurochem 104:993–1005CrossRefGoogle Scholar
  95. 95.
    Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (2001) Activation of Caspase-12, an endoplasmic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276:13935–13940PubMedGoogle Scholar
  96. 96.
    Morishima N, Nakanishi K, Takenouchi H, Shibata T, Yasuhiko Y (2002) An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem 277:34287–34294PubMedCrossRefGoogle Scholar
  97. 97.
    Rao RV, Castro-Obregon S, Frankowski H, Schuler M, Stoka V, del Rio G, Bredesen DE, Ellerby HM (2002) Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J Biol Chem 277:21836–21842PubMedCrossRefGoogle Scholar
  98. 98.
    Fujita E, Kouroku Y, Jimbo A, Isoai A, Maruyama K, Momoi T (2002) Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells. Cell Death Differ 9:1108–1114PubMedCrossRefGoogle Scholar
  99. 99.
    Nakagawa T, Yuan J (2000) Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol 150:887–894PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    de la Cadena SG, Hernández-Fonseca K, Camacho-Arroyo I, Massieu L (2014) Glucose deprivation induces reticulum stress by the PERK pathway and caspase-7- and calpain-mediated caspase-12 activation. Apoptosis 19:414–427PubMedCrossRefGoogle Scholar
  101. 101.
    Martinez JA, Zhang Z, Svetlov SI, Hayes RL, Wang KK, Larner SF (2010) Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells. Apoptosis 15:1480–1493PubMedCrossRefGoogle Scholar
  102. 102.
    Rao RV, Hermel E, Castro-Obregon S, Del Rio G, Ellerby LM, Ellerby HM, Bredesen DE (2001) Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 276:33869–33874PubMedCrossRefGoogle Scholar
  103. 103.
    Heath-Engel HM, Chang NC, Shore GC (2008) The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene 27:6419–6433PubMedCrossRefGoogle Scholar
  104. 104.
    Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS (2003) Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors. J Biol Chem 278:20915–20924PubMedCrossRefGoogle Scholar
  105. 105.
    Kikuchi S, Shinpo K, Tsuji S, Yabe I, Niino M, Tashiro K (2003) Brefeldin A-induced neurotoxicity in cultured spinal cord neurons. J Neurosci Res 71:591–599PubMedCrossRefGoogle Scholar
  106. 106.
    Obeng EA, Boise LH (2005) Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. J Biol Chem 280:29578–29587PubMedCrossRefGoogle Scholar
  107. 107.
    Di Sano F, Ferraro E, Tufi R, Achsel T, Piacentini M, Cecconi F (2006) Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism. J Biol Chem 281:2693–2700PubMedCrossRefGoogle Scholar
  108. 108.
    Matsuzaki S, Hiratsuka T, Kuwahara R, Katayama T, Tohyama M (2010) Caspase-4 is partially cleaved by calpain via the impairment of Ca2+ homeostasis under the ER stress. Neurochem Int 56:352–356PubMedCrossRefGoogle Scholar
  109. 109.
    Yukioka F, Matsuzaki S, Kawamoto K, Koyama Y, Hitomi J, Katayama T, Tohyama M (2008) Presenilin-1 mutation activates the signaling pathway of caspase-4 in endoplasmic reticulum stress-induced apoptosis. Neurochem Int 52:683–687PubMedCrossRefGoogle Scholar
  110. 110.
    Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, Manabe T, Yamagishi S, Bando Y, Imaizumi K, Tsujimoto Y, Tohyama M (2004) Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Aβ-induced cell death. J Cell Biol 165:347–356PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Binet F, Chiasson S, Girard D (2010) Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils. Biochem Biophys Res Commun 391:18–23PubMedCrossRefGoogle Scholar
  112. 112.
    Bian ZM, Elner SG, Elner VM (2009) Dual involvement of caspase-4 in inflammatory and ER stress-induced apoptotic responses in human retinal pigment epithelial cells. Investig Ophthalmol Vis Sci 50:6006–6014CrossRefGoogle Scholar
  113. 113.
    Mouw G, Zechel JL, Gamboa J, Lust WD, Selman WR, Ratcheson RA (2003) Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat. Neuroreport 14:183–186PubMedCrossRefGoogle Scholar
  114. 114.
    Nakka VP, Gusain A, Raghubir R (2010) Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats. Neurotox Res 17:189–202PubMedCrossRefGoogle Scholar
  115. 115.
    Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J (2005) A Selective inhibitor of eIF2α dephosphorylation protects cells from ER stress. Science 307:935–939PubMedCrossRefGoogle Scholar
  116. 116.
    Sokka AL, Putkonen N, Mudo G, Pryazhnikov E, Reijonen S, Khiroug L, Belluardo N, Lindholm D, Korhonen L (2007) Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain. J Neurosci 27:901–908PubMedCrossRefGoogle Scholar
  117. 117.
    Shibata M, Hattori H, Sasaki T, Gotoh J, Hamada J, Fukuuchi Y (2003) Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice. Neuroscience 118:491–499PubMedCrossRefGoogle Scholar
  118. 118.
    Liu HJ, Yang JP, Wang CH, Liu RC, Li Y, Li CY (2009) Endoplasmic reticulum in the penumbra following middle cerebral artery occlusion in the rabbit. Neurol Sci 30:227–232PubMedCrossRefGoogle Scholar
  119. 119.
    Zhu H, Zhu H, Xiao S, Sun H, Xie C, Ma Y (2012) Activation and crosstalk between the endoplasmic reticulum road and JNK pathway in ischemia-reperfusion brain injury. Acta Neurochir 154:1197–1203PubMedCrossRefGoogle Scholar
  120. 120.
    Larner SF, Hayes RL, McKinsey DM, Pike BR, Wang KKW (2004) Increased expression and processing of caspase-12 after traumatic brain injury in rats. J Neurochem 88:78–90PubMedCrossRefGoogle Scholar
  121. 121.
    Badiola N, Penas C, Miñano-Molina A, Barneda-Zahonero B, Fadó R, Sánchez-Opazo G, Comella JX, Sabriá J, Zhu C, Blomgren K, Casas C, Rodríguez-Alvarez J (2011) Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12. Cell Death Dis 2:1–8CrossRefGoogle Scholar
  122. 122.
    Chen X, Kintner DB, Luo J, Baba A, Matsuda T, Sun D (2008) Endoplasmic reticulum Ca2+ dysregulation and endoplasmic reticulum stress following in vitro neuronal ischemia: role of Na+-K+-Cl cotransporter. J Neurochem 106:1563–1576PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Zhang A, Zhang J, Sun P, Yao C, Su C, Sui T, Huang H, Cao X, Ge Y (2010) EIF2α and caspase-12 activation are involved in oxygen–glucose–serum deprivation/restoration-induced apoptosis of spinal cord astrocytes. Neurosci Lett 478:32–36PubMedCrossRefGoogle Scholar
  124. 124.
    D’Osualdo AD, Anania VG, Yu K, Lill JR, Kaufman RJ, Matsuzawa S, Reed JC (2015) Transcription factor ATF4 induces NLRP1 inflammasome expression during endoplasmic reticulum stress. PLoS One 10:1–16CrossRefGoogle Scholar
  125. 125.
    Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, Shen S, Nguyen V, Backes BJ, Heiman M, Heintz N, Greengard P, Hui S, Tang Q, Trusina A, Oakes SA, Papa FR (2012) IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 16:250–264PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Bronner DN, Abuaita BH, Chen X, Fitzgerald KA, Nuñez G, He Y, Yin XM, O’Riordan MX (2015) Endoplasmic reticulum stress activates the inflammasome via NLRP3-and caspase-2-driven mitochondrial damage. Immunity 43:451–462PubMedCrossRefGoogle Scholar
  127. 127.
    Lu M, Sun XL, Qiao C, Liu Y, Ding JH, Hu G (2014) Uncoupling protein 2 deficiency aggravates astrocytic endoplasmic reticulum stress and nod-like receptor protein 3 inflammasome activation. Neurobiol Aging 35:421–430PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMéxicoMexico

Personalised recommendations