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-X1

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.

Characterization and expression analysis of Paralichthys olivaceus voltage-dependent anion channel (VDAC) gene in response to virus infection

“…Recent studies indicated that VDAC plays an important role in drug-induced apoptosis [11,17]. It is known that arsenic trioxide could induce the upregulation of VDAC in apoptotic human myeloma cells and increased expression of VDAC is correlated with mouse uterine epithelial apoptosis [9,39]. Taken together, our results suggested that PoVDAC might be mediated fish antiviral immune response through induction of apoptosis.…”

Fos Plays No Role in Apoptosis of Epithelia in the Mouse Male Accessory Sex Organs and Uterus

“…Depletion of these steroid hormones induces apoptosis of epithelial cells in these organs [1][2][3][4][5][6][7][8][9]. Although this phenomenon is well recognized, the mechanism of the signal transduction in initiation of apoptosis has not been fully elucidated [4,6,[8][9][10].…”

Bcl-xL and Mcl-1 are involved in prevention of in vitro apoptosis in rat late-stage erythroblasts derived from bone marrow

“…Given that anti-and pro-apoptotic members interact with each other to suppress the activity of their partners (Bras et al, 2005;Oltvai et al, 1993;Willis and Adams, 2005), the ratios of protein or mRNA abundance between them are considered to be important factors in control of apoptosis (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Lynch et al, 2010;Mei et al, 2007;Takagi-Morishita et al, 2003;Viola-Rhenals et al, 2007;Xu et al, 2007). Actually, several studies had demonstrated that enhancement of the mRNA ratios of Bax, Bak and Bad to Bcl-xL were associated with the efficient induction of cellular apoptosis (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Takagi-Morishita et al, 2003;Xu et al, 2007). Similarly in the present study, EPO stimulation resulted in decreases in the mRNA ratios of Bax, Bak, and Bad to Bcl-xL, and concomitant reduction in apoptosis of late-stage erythroblasts.…”

“…Cell death is then induced through the activation of a cascade between caspase-9 and caspase-3 (Elmore, 2007). The balance of protein or mRNA abundance between the Bcl-2 family members is believed to regulate apoptosis and presumably determine the cell fate (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Lynch et al, 2010;Mei et al, 2007;Takagi-Morishita et al, 2003;Viola-Rhenals et al, 2007;Xu et al, 2007). In particular, it is known that Bcl-xL plays an important role as an antiapoptotic factor in erythropoiesis (Dolznig et al, 2002;Gregoli and Bondurant, 1997;Testa, 2004).…”