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      ROS-mediated oligomerization of VDAC2 is associated with quinocetone-induced apoptotic cell death.

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          Abstract

          Quinocetone (QCT) has been approved and widely used as an animal feed additive in China since 2003. However, investigations indicate that QCT shows potential toxicity both in vitro and in vivo. Although voltage dependent anion channel 1 (VDAC1) involved in regulating QCT-induced apoptotic cell death has been established, the role of voltage dependent anion channel 2 (VDAC2) in QCT-induced toxicity remains unclear. In this study, we showed that QCT-induced cell death was coupled to VDAC2 oligomerization. Moreover, VDAC inhibitor 4, 4'-diisothiocyano stilbene-2, 2'-disulfonic acid (DIDS) alleviated QCT-induced cell death and VDAC2 oligomerization. Meanwhile, overexpression VDAC2 aggravated QCT-induced VDAC2 oligomerization. In addition, caspase inhibitor Z-VAD-FMK and reactive oxidative species (ROS) scavenger N-acetyl-l-cysteine (NAC) apparently blocked QCT-induced cell death and VDAC2 oligomerization. Finally, overexpression N-terminal truncated VDAC2 attenuated QCT-induced VDAC2 oligomerization but had no influence on its localization to mitochondria when comparing to the full length of VDAC2. Taken together, our results reveal that ROS-mediated VDAC2 oligomerization is associated with QCT-induced apoptotic cell death. The N-terminal region of VDAC2 is required for QCT-induced VDAC2 oligomerization.

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          Author and article information

          Journal
          Toxicol In Vitro
          Toxicology in vitro : an international journal published in association with BIBRA
          Elsevier BV
          1879-3177
          0887-2333
          Mar 2018
          : 47
          Affiliations
          [1 ] Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanminyuan West Road No. 2, Beijing, Haidian District 100193, China.
          [2 ] Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanminyuan West Road No. 2, Beijing, Haidian District 100193, China. Electronic address: xiaoxl@cau.edu.cn.
          Article
          S0887-2333(17)30371-5
          10.1016/j.tiv.2017.12.005
          29229420
          1b2501ae-6eb2-4fab-83d4-be51bb6b35c7
          History

          Reactive oxygen species,VDAC2 oligomerization,Cell death,Quinocetone

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