Caspase-independent death of meiotic and postmeiotic cells overexpressing p53: calpain involvement

Cell Death and Differentiation
M CoureuilI Allemand

Abstract

In a model of male sterility (MTp53) owing to enforced p53 expression in spermatocytes II and spermatids of transgenic mice, we focused on the role of caspases. Most of them are expressed in all differentiation stages, but only the transcriptional levels of caspase-2 and caspase-3 are modified in MTp53 germ cells. In normal testis, cleaved caspase-3 and caspase-9 are detected during the elongation of spermatids. Despite this constitutive presence of caspases during terminal differentiation, calpains are the main effectors of germ cell loss in MTp53 testes: calpain 1 RNA levels are increased, caspase-3-like activity is markedly decreased while calpain activity is higher and the calpain inhibitor E64d ((2S, 3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester) reduces TUNEL labeling in MTp53 testis, whereas pancaspase inhibitor zVADfmk (N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone) has no effect. Our work suggests that despite the presence, and potent involvement, of caspases in male haploid cell maturation, calpains are the executioners of the death of terminally differentiating germ cells.

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Citations

Jan 2, 2007·Apoptosis : an International Journal on Programmed Cell Death·Carlos LizamaRicardo D Moreno
Dec 3, 2009·Médecine sciences : M/S·Pascale Cossart, Jean-François Bach
Dec 3, 2009·Médecine sciences : M/S·Vilma BarrocaPierre Fouchet
May 27, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Valeria MericoNori Tolosa de Talamoni
Mar 28, 2012·Human Reproduction·Hao ChenZhiming Cai
Nov 28, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Emilie ArnaultBrigitte Lefèvre
Apr 24, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Xiaohui CuiChangfa Wang
Oct 11, 2007·Molecular Reproduction and Development·Veronica A CodeliaRicardo D Moreno

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