ROS介导的VDAC2寡聚化与喹烯酮诱导的凋亡细胞死亡机制 | 翌圣生物

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.