H2S inhibits apo(a) expression and secretion through PKC/FXR and Akt/HNF4 pathways in HepG2 cells

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• 作者：Kai Qu ; Ya-mi Liu ; Xing-lan He ; Hai Zhang ; Kai Zhang ; Juan Peng ; Ya-ling Tang ; Xiao-hua Yu ; Jun-fa Zeng ; Jian-jun Lei ; Dang-heng Wei and Zuo Wang
• 刊名：Cell Biology International
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：40
• 期：8
• 页码：906-916
• 全文大小：1382K
• ISSN：1095-8355

文摘

Lipoprotein(a) [Lp(a)] is a strong genetic risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Hydrogen sulfide (H₂S), a member of the gas transmitter family, performs important biological actions, including protection against cardiovascular diseases and maintenance of the lipid metabolism equilibrium in hepatocytes and adipocytes. In this study, we investigated the possible molecular mechanism of H₂S that influences apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of H₂S on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. Results showed that H₂S significantly inhibited the expression and secretion levels of apo(a). These effects were attenuated by the PKCα inhibitor and FXR siRNA. H₂S also reduced HNF4α expression and enhanced FXR expression. The Akt inhibitor partially reversed H₂S-induced inhibition of apo(a) and HNF4α expression and apo(a) secretion. This study reveals that H₂S suppressed apo(a) expression and secretion via the PKCα-FXR and PI3K/Akt-HNF4α pathways.