DIDS inhibits overexpression BAK1‐induced mitochondrial apoptosis through GSK3β/β‐catenin signaling pathway. Issue 6 (15th January 2018)

• Record Type: Journal Article
• Authors: Yang, Xiayun; Tang, Shusheng; Li, Daowen; Yu, Xiaohong; Wang, Fuyun; Xiao, Xilong
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 6(2018:Jun.)
• Page Start: 5070
• Page End: 5077
• Publication Date: 2018-01-15
• Subjects: BAK1 -- DIDS -- GSK3β/β‐catenin -- mitochondrial apoptosis; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26396
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Bcl‐2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4, 4′‐diisothiocyanostilbene‐2, 2′‐disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1‐induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1‐induced apoptosis through GSK3β/β‐catenin signaling pathway. The results showed overexpression BAK1 in 293T cells induced mitochondrial apoptosis accompanied by increasing the expression levels of cleaved caspase‐9, ‐3, poly (ADP‐ribose) polymerase (PARP) and reducing the MMP. Furthermore, overexpression BAK1 decreased the expression levels of Ser9‐GSK3β and β‐catenin. In addition, lithium chloride (LiCl), an activator of Wnt/β‐catenin signaling pathway, markedly attenuated overexpression BAK1‐induced mitochondrial apoptosis by restoring the expression levels of Ser9‐GSK3β and β‐catenin. Finally, DIDS absolutely abolished overexpression BAK1‐mediated mitochondrial apoptosis through recovering the expression levels of Ser9‐GSK3β and β‐catenin. Taken together, our results reveal that DIDS blocks overexpression BAK1‐induced mitochondrial apoptosis through GSK3β/β‐catenin pathway. Abstract : Wnt/β‐catenin signaling is involved in overexpression BAK1‐induced mitochondrial apoptosis through GSK3β dependent pathway. DIDS abrogates overexpression BAK1‐mediated mitochondrial apoptosis through GSK3β/β‐catenin pathway.