Aromatase Deficiency Inhibits the Permeability Transition in Mouse Liver Mitochondria

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 醫學院 > 癌症生物學研究所 > 期刊論文 > Item 310903500/31198

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题名:	Aromatase Deficiency Inhibits the Permeability Transition in Mouse Liver Mitochondria
作者:	(Loredana Moro);(Arnaldo A. Arbini);謝哲宗(Jer-Tsong Hsieh);(Jeffery Ford);(Evan R. Simpson);(Asghar Hajibeigi);(Orhan K. Oz)
贡献者:	醫學院癌症生物學研究所
日期:	2010-04
上传时间:	2010-09-27 15:46:35 (UTC+8)
摘要:	Lack of estrogens affects male physiology in a number of ways, including severe changes in liver metabolism that result in lipid accumulation and massive hepatic steatosis. Here we investigated whether estrogen deficiency may alter the functionality and permeability properties of liver mitochondria using, as an experimental model, aromatase knockout (ArKO) male mice, which cannot synthesize endogenous estrogens due to a disruption of the Cyp19 gene. Liver mitochondria isolated from ArKO mice displayed increased activity of the mitochondrial respiratory complex IV compared with wild-type mice and were less prone to undergo cyclosporin A-sensitive mitochondrial permeability transition (MPT) induced by calcium loading. The altered permeability properties of the mitochondrial membranes were not due to changes in reactive oxygen species, ATP levels, or mitochondrial membrane potential but were associated with increased content of the phospholipid cardiolipin, structural component of the mitochondrial membranes and regulator of the MPT pore, and with increased mitochondrial protein levels of Bcl-2 and the adenine nucleotide translocator (ANT), regulator and component of the MPT pore, respectively. Real-time RT-PCR demonstrated increased mRNA levels for Bcl-2 and ANT2 but not for the ANT1 isoform in ArKO livers. Supplementation of 17β-estradiol retrieved ArKO mice from massive hepatic steatosis and restored mitochondrial permeability properties, cardiolipin, Bcl-2, and ANT2 levels. Overall, our findings demonstrate an important role of estrogens in the modulation of hepatic mitochondrial function and permeability properties in males and suggest that estrogen deficiency may represent a novel positive regulator of Bcl-2 and ANT2 proteins, two inhibitors of MPT occurrence and powerful antiapoptotic molecules.
關聯:	ENDOCRINOLOGY 151(4):1643-1652
显示于类别:	[癌症生物學研究所] 期刊論文

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