title: Redistribution of Bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia.
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.
authors.affiliation: Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Yamamoto
authors.forename: A P
authors.initials: AP
authors.lastname: Sinha Hikim
authors.forename: P N
authors.initials: PN
authors.lastname: Huynh
authors.forename: B
authors.initials: B
authors.lastname: Shapiro
authors.forename: Y
authors.initials: Y
authors.lastname: Lue
authors.forename: W A
authors.initials: WA
authors.lastname: Salameh
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: R S
authors.initials: RS
authors.lastname: Swerdloff
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D005334:Fever / Q000378:metabolism* / Q000473:pathology*; D005854:Germ Cells / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012670:Seminiferous Epithelium / Q000166:cytology / Q000254:growth & development; D013737:Testis / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology; D051028:bcl-2-Associated X Protein
chemical_list: C494827:Bax protein, mouse; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein