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Issue 3, 2017
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The UCP2-related mitochondrial pathway participates in rhein-induced apoptosis in HK-2 cells

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Abstract

Rhein is one of the main active compounds in total rhubarb anthraquinones (TRAs) that were reported to cause nephrotoxicity. This paper explored the mechanism of how rhein induced apoptosis in human renal proximal tubular epithelial cells (HK-2 cells). In this study, rhein was found to induce apoptosis in HK-2 cells according to the results of annexin V/PI staining assay. The underlying mechanisms were investigated, and the mitochondria-mediated pathway was found to be critical. A series of related biological events were explored, including the disruption of mitochondrial membrane potential (MMP), the decrease of the ATP level, the release of cytochrome c (Cyt-c) from the mitochondrion to the cytosol, and down-regulation of Bcl-2 and up-regulation of Bax. Furthermore, rhein significantly increased the levels of ROS and inhibited the expression of mitochondrial uncoupling protein 2 (UCP2). UCP2 inhibition dramatically boosted oxidative stress and exacerbated rhein-induced apoptosis, whereas co-incubation with an ROS scavenger N-acetylcysteine (NAC) could decrease rhein-induced apoptosis. In conclusion, our results have demonstrated that rhein induced apoptosis in HK-2 cells via the UCP2-related mitochondrial pathway and rhein might be a weak inhibitor of UCP2. Our findings provide new evidence that UCP2 plays an important role in the mitochondrial apoptotic pathway.

Graphical abstract: The UCP2-related mitochondrial pathway participates in rhein-induced apoptosis in HK-2 cells

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Publication details

The article was received on 02 Nov 2016, accepted on 04 Feb 2017 and first published on 06 Feb 2017


Article type: Paper
DOI: 10.1039/C6TX00410E
Citation: Toxicol. Res., 2017,6, 297-304
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    The UCP2-related mitochondrial pathway participates in rhein-induced apoptosis in HK-2 cells

    Y. Mao, M. Zhang, J. Yang, H. Sun, D. Wang, X. Zhang, F. Yu and J. Li, Toxicol. Res., 2017, 6, 297
    DOI: 10.1039/C6TX00410E

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