Caspase-independent death of meiotic and postmeiotic cells overexpressing p53: calpain involvement
Male
0301 basic medicine
Cell Death
Calpain
Caspase 3
Molecular Sequence Data
Caspase 2
Gene Expression
Mice, Transgenic
Spermatids
Caspase 9
Gene Expression Regulation, Enzymologic
Enzyme Activation
Meiosis
Mice
03 medical and health sciences
Caspases
Animals
Amino Acid Sequence
RNA, Messenger
Sequence Alignment
Infertility, Male
DOI:
10.1038/sj.cdd.4401887
Publication Date:
2006-03-10T10:13:35Z
AUTHORS (8)
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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