title: Mouse uterine epithelial apoptosis is associated with expression of mitochondrial voltage-dependent anion channels, release of cytochrome C from mitochondria, and the ratio of Bax to Bcl-2 or Bcl-X.
abstract: The release of cytochrome c from mitochondria, which is regulated by Bcl-2 family members and is considered to take place through voltage-dependent anion channels (VDACs) on the outer membranes of mitochondria, results in activation of effector caspases, such as caspase-3, which induce apoptosis. We studied the involvement of the mitochondrial apoptosis pathway in uterine epithelial apoptosis. Estradiol-17beta pellets were implanted into ovariectomized mice and removed 4 days later (Day 0). The apoptotic index (percentage of apoptotic cells) of the luminal epithelium increased markedly, peaking on Day 2, whereas that of the glandular epithelium increased much less. Expression of VDAC1, 2, and 3 mRNAs increased in the luminal epithelium in correlation with the apoptotic index of the luminal epithelium. No increases in VDAC1, 2, and 3 mRNA levels were observed in the stroma or muscle, where no apoptosis occurs. VDAC1 protein levels in the uterus also correlated well with the apoptotic index of the luminal epithelium. In addition, the apoptotic index showed good correlation with the release of cytochrome c from mitochondria, activation of caspase-3, which was immunohistochemically detected only in the epithelium, and the mRNA and protein ratios of Bax:Bcl-2 and Bax:Bcl-X in the uterus. The present results suggest that the release of cytochrome c from mitochondria, which is regulated by Bcl-2 family members, plays a role in uterine epithelial apoptosis after estrogen deprivation. The increase in VDAC expression may facilitate the release of cytochrome c during apoptosis.
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Takagi-Morishita
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamada
authors.forename: Ayako
authors.initials: A
authors.lastname: Sugihara
authors.forename: Teruo
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000502:physiology; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005420:Flavoproteins / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014599:Uterus / Q000502:physiology*; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D051033:Apoptosis Inducing Factor; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D004967:Estrogens; D005420:Flavoproteins; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C494830:AIFM1 protein, mouse; D018272:Porins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C494763:Vdac1 protein, mouse; C480078:Vdac3 protein, mouse; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D050995:Voltage-Dependent Anion Channel 1; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases