Key apoptotic pathways for heat-induced programmed germ cell death in the testis.
Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.
Hikim
Amiya P Sinha
AP
Division of Endocrinology, Department of Medicine, Harbor-University of California-Los Angeles Medical Center, Box 446, 1000 West Carson Street, Torrance, CA 90509, USA. hikim@gcrc.rei.edu
Lue
Yanhe
Y
Yamamoto
Cindy M
CM
Vera
Yanira
Y
Rodriguez
Susana
S
Yen
Pauline H
PH
Soeng
Kevin
K
Wang
Christina
C
Swerdloff
Ronald S
RS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D053222:Fas Ligand Protein; D006358:Hot Temperature; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D013090:Spermatocytes / Q000201:enzymology* / Q000648:ultrastructure; D013737:Testis / Q000166:cytology* / Q000201:enzymology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C494828:Bax protein, rat; D003574:Cytochrome c Group; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; C505516:Casp6 protein, mouse; C505518:Casp6 protein, rat; C505524:Casp7 protein, mouse; C506434:Casp9 protein, mouse; C506435:Casp9 protein, rat; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases