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PMID:11090436
| Citation |
Yamamoto, CM, Sinha Hikim, AP, Huynh, PN, Shapiro, B, Lue, Y, Salameh, WA, Wang, C and Swerdloff, RS (2000) Redistribution of Bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia. Biol. Reprod. 63:1683-90 |
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| Abstract |
Programmed cell death occurs spontaneously during spermatogenesis and can be induced in a cell- and stage-specific manner by mild testicular hyperthermia. Studies using transgenic mice suggest the involvement of Bcl-2 proteins in regulating germ cell apoptosis. To delineate further the pathways involved, we examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in rat testes after transient exposure to heat (43 degrees C for 15 min). Germ cell apoptosis, involving exclusively early (I-IV) and late (XII-XIV) stages, was activated within 6 h. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to perinuclear localization within 0.5 h of heating as assessed by immunocytochemical methods. In contrast, Bcl-2 is distributed both in the cytoplasm and nucleus in those cell types susceptible to heat-induced apoptosis. Despite the striking redistribution, Bax levels remained unchanged as determined by Western analysis; Bcl-2 levels increased significantly by 6 h after heat exposure. Reverse transcription-polymerase chain reaction analysis indicated no change in either Bax or Bcl-2 mRNA levels in response to heat, suggesting the involvement of post-transcriptional rather than transcriptional mechanisms mediating their activity. The marked subcellular redistribution of Bax prior to activation of apoptosis and the increase in Bcl-2 suggest an involvement of Bcl-2 family members in heat-induced apoptotic death of germ cells. |
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| Keywords |
Animals; Apoptosis/physiology; Base Sequence; Blotting, Western; Fever/metabolism; Fever/pathology; Germ Cells/metabolism; Germ Cells/pathology; Immunohistochemistry; Male; Mice; Molecular Sequence Data; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Seminiferous Epithelium/cytology; Seminiferous Epithelium/growth & development; Testis/metabolism; Testis/pathology; Up-Regulation/genetics; Up-Regulation/physiology; bcl-2-Associated X Protein |
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