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DIDS inhibits overexpression BAK1-induced mitochondrial apoptosis through GSK3β/β-catenin signaling pathway

Xiayun Yang1, Shusheng Tang1, Daowen Li1

  • 1Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, Haidian District, China.

Journal of Cellular Physiology
|December 13, 2017
PubMed

Insights

4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) prevents cell death induced by Bcl-2 homologous antagonist/killer (BAK1) overexpression. DIDS protects against BAK1-induced apoptosis by modulating the GSK3β/β-catenin signaling pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Bcl-2 homologous antagonist/killer (BAK1) is a key regulator of mitochondrial apoptosis.
  • The precise molecular mechanisms underlying BAK1-induced apoptosis are not fully understood.
  • 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) is known to protect cells from apoptosis.

Purpose of the Study:

  • To investigate whether DIDS can inhibit BAK1-induced mitochondrial apoptosis.
  • To explore the role of the GSK3β/β-catenin signaling pathway in DIDS's protective effect.

Main Methods:

  • Overexpression of BAK1 in 293T cells.
  • Analysis of apoptosis markers (cleaved caspase-9, -3, PARP) and mitochondrial membrane potential (MMP).
  • Assessment of GSK3β and β-catenin expression levels.
  • Treatment with DIDS and lithium chloride (LiCl).

Main Results:

  • BAK1 overexpression induced mitochondrial apoptosis, increasing cleaved caspase-9, -3, PARP, and decreasing MMP.
  • BAK1 overexpression reduced Ser9-GSK3β and β-catenin levels.
  • LiCl attenuated BAK1-induced apoptosis by restoring Ser9-GSK3β and β-catenin.
  • DIDS completely blocked BAK1-induced apoptosis by restoring Ser9-GSK3β and β-catenin.

Conclusions:

  • DIDS inhibits BAK1-induced mitochondrial apoptosis.
  • The protective mechanism of DIDS involves the GSK3β/β-catenin signaling pathway.
Keywords:
BAK1DIDSGSK3β/β-cateninmitochondrial apoptosis

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