Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells
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- 作者：Shatrunajay Shuklaa ; b ; Ankita Sharmaa ; Vivek Kumar Pandeya ; c ; Sheikh Raisuddinb ; Poonam Kakkara ; c ; kakkarp59@gmail.com" class="auth_mail" title="E-mail the corresponding author ; pkakkar@iitr.res.in" class="auth_mail" title="E-mail the corresponding author
- 关键词：BBR ; berberine ; NIC ; nicotinamide ; HepG2 ; human hepatocellular carcinoma cells ; HCC ; hepatocellular carcinoma ; SIR2 ; Silent Information regulator 2 ; FoxO ; forkhead-box that belong to the other (O) subfamily ; FoxO1 ; forkhead-box O 1 transcription factor ; FoxO3a ; forkhead-box O 3a transcription factor ; Bim ; BH3-only member of Bcl-2 family ; FBS ; fetal bovine serum ; ROS ; reactive oxygen species ; NAD+ ; nicotinamide adenine dinucleotide ; PI3K ; phosphatidylinositol-3-kinase ; PUMA ; p53 upregulated modul
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2016
- 出版时间：15 January 2016
- 年：2016
- 卷：291
- 期：Complete
- 页码：70-83
- 全文大小：2843 K
文摘
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Berberine inhibits sirtuins at transcriptional as well as at translational level.
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10">Sirtuins inhibition leads to acetylation of non-histone proteins, FoxO1/3a and p53.
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15">Acetylated FoxO and p53 transcriptionally upregulate BH3-only proteins Bim and PUMA respectively.
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BH3-only proteins trigger mitochondrial dysfunction culminating into apoptosis.
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SRT-1720 (SIRT-1 activator) partially restores Bax/Bcl-2 ratio and reduces berberine induced cytotoxicity in HepG2 cells.
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