心磷脂
胆汁淤积
线粒体
线粒体生物发生
化学
线粒体内膜
生物化学
活性氧
抗氧化剂
线粒体通透性转换孔
β氧化
脂肪生成
生物
酶
内分泌学
脂质代谢
磷脂
细胞凋亡
程序性细胞死亡
膜
作者
Gaetano Serviddio,Francesco Bellanti,Eleonora Stanca,Paola Lunetti,Maria Blonda,Rosanna Tamborra,Luisa Siculella,Gianluigi Vendemiale,Loredana Capobianco,Anna Maria Giudetti
标识
DOI:10.1016/j.freeradbiomed.2014.05.002
摘要
The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property.
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