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Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells

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Abstract

Previously, we analyzed mice lacking either caspase-2 or caspase-3 and documented a role for caspase-2 in developmental and chemotherapy-induced apoptosis of oocytes. Those data also revealed dispensability of caspase-3, although we found this caspase critical for ovarian granulosa cell death. Because of the mutual interdependence of germ cells and granulosa cells, herein we generated caspase-2 and -3 double-mutant (DKO) mice to evaluate how these two caspases functionally relate to each other in orchestrating oocyte apoptosis. No difference was observed in the rate of spontaneous oocyte apoptosis between DKO and wildtype (WT) females. In contrast, the oocytes from DKO females were more susceptible to apoptosis induced by DNA damaging agents, compared with oocytes from WT females. This increased sensitivity to death of DKO oocytes appears to be a specific response to DNA damage, and it was associated with a compensatory upregulation of caspase-12. Interestingly, DKO oocytes were more resistant to apoptosis induced by methotrexate (MTX) than WT oocytes. These results revealed that in female germ cells, insults that directly interfere with their metabolic status (e.g. MTX) require caspase-2 and caspase-3 as obligatory executioners of the ensuing cell death cascade. However, when DNA damage is involved, and in the absence of caspase-2 and -3, caspase-12 becomes upregulated and mediates apoptosis in oocytes.

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Abbreviations

BSA:

bovine serum albumin

DKO:

double knockout

DXR:

doxorubicin

eCG:

equine chorionic gonadotropin

ER:

endoplasmic reticulum

hCG:

human chorionic gonadotropin

HTF:

human tubal fluid

LPS:

bacterial lipopolysaccharide

MTX:

methotrexate

PCD:

programmed cell death

WT:

wildtype

z-VAD:

pancaspase inhibitor

References

  1. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  PubMed  CAS  Google Scholar 

  2. Fadeel B, Orrenius S (2005) Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med 258:479–517

    Article  PubMed  CAS  Google Scholar 

  3. Krantic S, Mechawar N, Reix S, Quirion R (2005) Molecular basis of programmed cell death involved in neurodegeneration. Trends Neurosci 28:670–676

    PubMed  CAS  Google Scholar 

  4. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O’Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH (2005) An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435:677–681

    Article  PubMed  CAS  Google Scholar 

  5. Reed JC (2006) Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ [Epub ahead of print]

  6. Takeuchi O, Fisher J, Suh H, Harada H, Malynn BA, Korsmeyer SJ (2005) Essential role of BAX, BAK in B cell homeostasis and prevention of autoimmune disease. Proc Natl Acad Sci USA 102:11272–11277

    Article  PubMed  CAS  Google Scholar 

  7. Lamkanfi, M., Declercq W, Depuydt B, Kalai M, Saelens X, Vandenabeele P (2003) The caspase family. In Los M, Walczak H (eds.) Caspases—Their role in cell death and cell survival. Landes Bioscience and Kluwer Academic, New York, pp. 1–40

    Google Scholar 

  8. Lettre G, Hengartner MO (2006) Developmental apoptosis in C. elegans: a complex CEDnario. Nat Rev Mol Cell Biol 7:97–108

    Article  PubMed  CAS  Google Scholar 

  9. Tilly JL (2001) Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol 2:838–848

    Article  PubMed  CAS  Google Scholar 

  10. De Felici M, Di Carlo A, Pesce M, Iona S, Farrace MG, Piacentini M (1999) Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo. Cell Death Differ 6:908–915

    Article  CAS  Google Scholar 

  11. Jurisicova A, Latham K, Casper RF, Varmuza SL (1998) Expression and regulation of genes associated with cell death during murine preimplantation embryo development. Mol Reprod Dev 51:243–253

    Article  PubMed  CAS  Google Scholar 

  12. Kugu K, Ratts VS, Piquette GN, Tilly KI, Tao X-J, Martimbeau S, Aberdeen GW, Krajewski S, Reed JC, Pepe GJ, Albrecht ED, Tilly JL (1998) Analysis of apoptosis and expression of bcl-2 gene family members in the human and baboon ovary. Cell Death Differ 5:67–76

    Article  PubMed  CAS  Google Scholar 

  13. Tilly JL, Tilly KI, Kenton ML, Johnson AL (1995) Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger RNA levels. Endocrinology 136:232–241

    Article  PubMed  CAS  Google Scholar 

  14. Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL (1999) Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat Genet 21:200–203

    Article  PubMed  CAS  Google Scholar 

  15. Perez GI, Trbovich AM, Gosden RG, Tilly JL (2000) Mitochondria and the death of oocytes. Nature 403:500–501

    Article  PubMed  CAS  Google Scholar 

  16. Yuan J (2006) Divergence from a dedicated cellular suicide mechanism: exploring the evolution of cell death. Mol Cell 23:1–12

    Article  PubMed  CAS  Google Scholar 

  17. Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A, Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL, Yuan J (1998) Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev 12:1304–1314

    PubMed  CAS  Google Scholar 

  18. Matikainen T, Perez GI, Zheng TS, Kluzak TR, Rueda BR, Flavell RA, Tilly JL (2001) Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology 142:2468–2480

    Article  PubMed  CAS  Google Scholar 

  19. Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384:368–372

    Article  PubMed  CAS  Google Scholar 

  20. 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-beta. Nature 403:98–103

    Article  PubMed  CAS  Google Scholar 

  21. Jurisicova A, Lee HJ, D’Estaing SG, Tilly JL, Perez GI (2006) Molecular requirements for doxorubicin-mediated death in murine oocytes. Cell Death Differ Jan 27 [Epub ahead of print]

  22. Morita Y, Perez GI, Paris F, Miranda SR, Ehleiter D, Haimovitz-Friedman A, Fuks Z, Xie Z, Reed JC, Schuchman EH, Kolesnick RN, Tilly JL (2000) Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 6:1109–1114

    Article  PubMed  CAS  Google Scholar 

  23. Perez GI, Tao XJ, Tilly JL (1999) Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes. Mol Hum Reprod 5:414–420

    Article  PubMed  CAS  Google Scholar 

  24. Jurisicova A, Antenos M, Varmuza S, Tilly JL, Casper RF (2003) Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation. Mol Hum Reprod 9:133–141

    Article  PubMed  CAS  Google Scholar 

  25. 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 9:1108–1114

    Article  PubMed  CAS  Google Scholar 

  26. Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325–337

    Article  PubMed  CAS  Google Scholar 

  27. Besnault-Mascard L, Leprince C, Auffredou MT, Meunier B, Bourgeade MF, Camonis J, Lorenzo HK, Vazquez A (2005) Caspase-8 sumoylation is associated with nuclear localization. Oncogene 24:3268–3273

    Article  PubMed  CAS  Google Scholar 

  28. Feng Y, Hu J, Xie D, Qin J, Zhong Y, Li X, Xiao W, Wu J, Tao D, Zhang M, Zhu Y, Song Y, Reed E, Li QQ, Gong J (2005) Subcellular localization of caspase-3 activation correlates with changes in apoptotic morphology in MOLT-4 leukemia cells exposed to X-ray irradiation. Int J Oncol 27:699–704

    PubMed  CAS  Google Scholar 

  29. Lakhani SA, Masud A, Kuida K, Porter GA Jr, Booth CJ, Mehal WZ, Inayat I, Flavell RA (2006) Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science 311:785–786

    Article  Google Scholar 

  30. Ruiz-Vela A, Opferman JT, Cheng EH, Korsmeyer SJ (2005) Proapoptotic BAX and BAK control multiple initiator caspases. EMBO Rep 6:379–385

    Article  PubMed  CAS  Google Scholar 

  31. Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115:2656–2664

    Article  PubMed  CAS  Google Scholar 

  32. Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan J, Thompson CB (2003) Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 162:59–69

    Article  PubMed  CAS  Google Scholar 

  33. Lamkanfi M, Kalai M, Vandenabeele P (2004) Caspase-12: an overview. Cell Death Differ 11:365–368

    Article  PubMed  CAS  Google Scholar 

  34. Cheung HH, Lynn-Kelly N, Liston P, Korneluk RG (2006) Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: A role for the IAPs. Exp Cell Res 312:2347–2357

    Article  PubMed  CAS  Google Scholar 

  35. Eichenlaub-Ritter U (1996) Parental age-related aneuploidy in human germ cells and offspring: a story of past and present. Environ Mol Mutagen 28:211–236

    Article  PubMed  CAS  Google Scholar 

  36. Kirkwood TBL (1998) Ovarian ageing and the general biology of senescence. Maturitas 30:105–111

    Article  PubMed  CAS  Google Scholar 

  37. Lim AST, Tsakok MFH (1997) Age-related decline in fertility: a link to degenerative oocytes? Fertility and Sterility 68:265–271

    Article  PubMed  CAS  Google Scholar 

  38. Wu J, Zhang L, Wang X (2000) Maturation and apoptosis of human oocytes in vitro are age-related. Fertil Steril 74:1137–1141

    Article  PubMed  CAS  Google Scholar 

  39. 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 Aß-induced cell death. J Cell Biol 165:347–356.

    Article  PubMed  CAS  Google Scholar 

  40. Fischer H, Koenig U, Eckhart L, Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 293:722–726

    Article  PubMed  CAS  Google Scholar 

  41. Zheng TS, Hunot S, Kuida K, Momoi T, Srinivasan A, Nicholson DW, Lazebnik Y, Flavell RA (2000) Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation. Nat Med 6:1241–1247

    Article  PubMed  CAS  Google Scholar 

  42. Fischer U, Schulze-Osthoff K (2005) Apoptosis-based therapies and drug targets. Cell Death Differ 12:942–961

    Article  PubMed  CAS  Google Scholar 

  43. Chan SL, Yu VC (2004) Proteins of the bcl-2 family in apoptosis signalling: from mechanistic insights to therapeutic opportunities. Clin Exp Pharmacol Physiol 31:119–128

    Article  PubMed  CAS  Google Scholar 

  44. Sah NK, Khan Z, Khan GJ, Bisen PS (2006) Structural, functional and therapeutic biology of survivin. Cancer Lett Apr 16 [Epub ahead of print]

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Acknowledgments

Supported by the Department of Physiology Michigan State University (GIP), and Vincent Research Funds, Massachusetts General Hospital (GIP). During these studies the following research fellows were supported by various institutions: Y Takai by the Department of OB/GYN, University of Tokyo, Faculty of Medicine (Tokyo, Japan); T Matikainen by the Finnish Foundation for Pediatric Research and the Finnish Cultural Foundation; A Jurisicova was supported by a New Investigator Salary Award from the Canadian Institutes of Health Research; MR Kim by the Department of OB/GYN, The Catholic University of Korea (Seoul, Korea). We would like to thank Mr. Sam Riley (Photo Lab, MGH) for outstanding assistance with the preparation of figures and image analysis.

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Authors and Affiliations

  1. Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 02114, USA

    Y. Takai, T. Matikainen, M. R. Kim, A. M. Trbovich & J. L. Tilly

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada

    A. Jurisicova

  3. Divisions of Development and Differentiation, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan

    E. Fujita & T. Momoi

  4. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    T. Nakagawa & J. Yuan

  5. Division of Cellular and Molecular Biology, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Ontario, Canada

    B. Lemmers & R. Hakem

  6. Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06510, USA

    R. A. Flavell

  7. Department of Physiology, Michigan State University, 4173 BPS, East Lansing, Michigan, 48824, USA

    G. I. Perez

Authors
  1. Y. Takai
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  2. T. Matikainen
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  5. A. M. Trbovich
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  7. T. Nakagawa
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  8. B. Lemmers
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  10. R. Hakem
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  11. T. Momoi
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  12. J. Yuan
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  13. J. L. Tilly
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  14. G. I. Perez
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Corresponding author

Correspondence to G. I. Perez.

Additional information

Takai and Matikainen contributed equally to this work.

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Takai, Y., Matikainen, T., Jurisicova, A. et al. Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Apoptosis 12, 791–800 (2007). https://doi.org/10.1007/s10495-006-0022-z

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