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Mitochondria-dependent pathway is involved in heat-induced male germ cell death: lessons from mutant mice.
- Source :
-
Biology of reproduction [Biol Reprod] 2004 May; Vol. 70 (5), pp. 1534-40. Date of Electronic Publication: 2004 Jan 28. - Publication Year :
- 2004
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Abstract
- The signaling events leading to apoptosis can be divided into two major pathways, involving either mitochondria (intrinsic) or death receptors (extrinsic). In a recent study, we have shown the involvement of the mitochondria-dependent apoptotic pathway in heat-induced male germ cell apoptosis in the rat. In additional studies, using the gld (generalized lymphoproliferation disease) and lprcg (lymphoproliferation complementing gld) mice, which harbor loss-of-function mutations in Fas L and Fas, respectively, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system is not required for heat-induced germ cell apoptosis in the testis. In the present study, we have found that the initiation of apoptosis in wild-type mice was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. The relocation of Bax is accompanied by sequestration of ultracondensed mitochondria into paranuclear areas of apoptotic germ cells, cytosolic translocation of mitochondrial cytochrome c and DIABLO, and is associated with activation of the initiator caspase 9 and the executioner caspase 3. Similar events were also noted in both gld and lprcg mice. Taken together, these results indicate that the mitochondria-dependent pathway is the key apoptotic pathway for heat-induced male germ cell death in mice.
- Subjects :
- Animals
Apoptosis Regulatory Proteins
Biological Transport
Carrier Proteins metabolism
Caspase 3
Caspase 9
Caspases metabolism
Cell Nucleus metabolism
Cytochromes c metabolism
Cytoplasm metabolism
Cytosol metabolism
Enzyme Activation
Fas Ligand Protein
Lymphoproliferative Disorders genetics
Male
Membrane Glycoproteins genetics
Mice
Mice, Inbred MRL lpr
Mice, Inbred Strains genetics
Mitochondria metabolism
Mitochondrial Proteins metabolism
Mutation
Proto-Oncogene Proteins c-bcl-2 metabolism
Tissue Distribution
bcl-2-Associated X Protein
fas Receptor genetics
Apoptosis physiology
Hot Temperature
Mitochondria physiology
Spermatozoa physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3363
- Volume :
- 70
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biology of reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 14749299
- Full Text :
- https://doi.org/10.1095/biolreprod.103.024661