Dataset Information

Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells.

ABSTRACT: Oxidative stress is thought to be critical for the pathogenesis of hepatic steatosis and its progress to non-alcoholic steatohepatitis. Berberine (BBR) can improve hepatic steatosis. In this study, we investigated the role of BBR in ameliorating oxidative stress. Lipid accumulation was measured in the livers of C57BL/6 mice fed a high fat diet (HFD) or a normal diet for 8 weeks, then either received BBR or vehicle for the study duration. Nrf2 distribution was detected in male Sprague-Dawley rats' livers in vivo and in Huh7 cells in vitro. ROS generation and mitochondrial complex expression was measured in Huh7 cells. HepG2 cells were employed for the measurement of oxygen consumption rates. Our results showed that BBR reduced triglyceride accumulation in the liver of HFD-fed mice. The activation and nuclear distribution of Nrf2 was decreased in the hepatocytes of rats that received BBR treatment, while on a HFD. BBR also markedly reduced Nox2-dependent cytoplasmic ROS production and mitochondrial ROS production, which was mediated by the down-regulation of Complex I and III expression. In conclusion, BBR has a great potential to reduce the effects of oxidative stress, which likely contributes to its protective effect in inhibiting the progression of hepatic steatosis to steatohepatitis.

SUBMITTER: Sun Y

PROVIDER: S-EPMC5595831 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells.

Sun Yixuan Y Yuan Xinlu X Zhang Feifei F Han Yamei Y Chang Xinxia X Xu Xi X Li Yu Y Gao Xin X

Scientific reports 20170912 1

Oxidative stress is thought to be critical for the pathogenesis of hepatic steatosis and its progress to non-alcoholic steatohepatitis. Berberine (BBR) can improve hepatic steatosis. In this study, we investigated the role of BBR in ameliorating oxidative stress. Lipid accumulation was measured in the livers of C57BL/6 mice fed a high fat diet (HFD) or a normal diet for 8 weeks, then either received BBR or vehicle for the study duration. Nrf2 distribution was detected in male Sprague-Dawley rats ...[more]

PMID: 28900305

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Project description:AimOxidative stress induced by free fatty acids (FFA) contributes to metabolic syndrome-associated development of cardiovascular diseases, yet molecular mechanisms remain poorly understood. This study aimed at establishing whether phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and its subcellular location play a role in FFA-induced endothelial oxidative stress.ResultsExposing human endothelial cells (ECs) with FFA activated mammalian target of rapamycin (mTOR)/S6K pathway, and upon activation, S6K directly phosphorylated PTEN at S380. Phosphorylation of PTEN increased its interaction with its deubiquitinase USP7 in the nucleus, leading to PTEN deubiquitination and nuclear export. The reduction of PTEN in the nucleus, in turn, decreased p53 acetylation and transcription, reduced the expression of the p53 target gene glutathione peroxidase-1 (GPX1), resulting in reactive oxygen species (ROS) accumulation and endothelial damage. Finally, C57BL/6J mice fed with high-fat atherogenic diet (HFAD) showed PTEN nuclear export, decreased p53 and GPX1 protein expressions, elevated levels of ROS, and significant lesions in aortas. Importantly, inhibition of mTOR or S6K effectively blocked these effects, suggesting that mTOR/S6K pathway mediates HFAD-induced oxidative stress and vascular damage via PTEN/p53/GPX1 inhibition in vivo.InnovationOur study demonstrated for the first time that S6K directly phosphorylated PTEN at S380 under high FFA conditions, and this phosphorylation mediated FFA-induced endothelial oxidative stress. Furthermore, we showed that S380 phosphorylation affected PTEN monoubiquitination and nuclear localization, providing the first example of coordinated regulation of PTEN nuclear localization via phosphorylation and ubiquitination.ConclusionOur studies provide a novel mechanism by which hyperlipidemia causes vascular oxidative damage through the phosphorylation of PTEN, blocking of PTEN nuclear function, and inhibition of p53/GPX1 activity.

Dataset Information

Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells.

Publications

Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells.

Similar Datasets

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