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

Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Research Abstract Details 

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Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Abstract Text:

Y Takai,T Matikainen,A Jurisicova,M R Kim,A M Trbovich,E Fujita,T Nakagawa,B Lemmers,R A Flavell,R Hakem,T Momoi,J Yuan,J L Tilly,G I Perez,Y Takai,T Matikainen,A Jurisicova,M R Kim,A M Trbovich,E Fujita,T Nakagawa,B Lemmers,R A Flavell,R Hakem,T Momoi,J Yuan,J L Tilly,G I Perez,

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.

Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Publishing Authors By Initials

Y Takai,T Matikainen,A Jurisicova,MR Kim,AM Trbovich,E Fujita,T Nakagawa,B Lemmers,RA Flavell,R Hakem,T Momoi,J Yuan,JL Tilly,GI Perez,Y Takai,T Matikainen,A Jurisicova,MR Kim,AM Trbovich,E Fujita,T Nakagawa,B Lemmers,RA Flavell,R Hakem,T Momoi,J Yuan,JL Tilly,GI Perez,

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Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Apoptosis : an international journal on programmed

VOLUME: 12

Page Numbers: 791-800

Journal Abbreviation: Apoptosis

ISSN: 1360-8185

DAY: 12

MONTH: Apr

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 9712129

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Grant and Affiliation Information for Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells.

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

Country: United States

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MEDLINETA: Apoptosis

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