TMEM16A Activation Inhibits Autophagy in Dorsal Root Ganglion Cells, Which is Associated with the p38 MAPK/mTOR Pathway

Cell Mol Neurobiol. 2024 Dec 4;45(1):1. doi: 10.1007/s10571-024-01507-z.

Abstract

Transmembrane member 16A (TMEM16A) exhibits a negative correlation with autophagy, though the underlying mechanism remains elusive. This study investigates the mechanism between TMEM16A and autophagy by inducing autophagy in DRG neuronal cells using Rapamycin. Results indicated that TMEM16A interference augmented cell viability and reduced Rapamycin-induced apoptosis. Autophagosome formation increased with TMEM16A interference but decreased upon overexpression. A similar increase in autophagosomes was observed with SB203580 treatment. Furthermore, TMEM16A interference suppressed Rapamycin-induced gene and protein expression of p38 MAPK and mTOR, whereas overexpression had the opposite effect. These findings suggest that TMEM16A activation inhibits autophagy in DRG cells, which is associated with the p38 MAPK/mTOR pathway, offering a potential target for mitigating neuropathic pain (NP).

Keywords: Autophagy; Dorsal root ganglia; Neuropathic pain; P38 MAPK; TMEM16A; mTOR.

MeSH terms

  • Animals
  • Anoctamin-1* / metabolism
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Autophagy* / drug effects
  • Autophagy* / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Ganglia, Spinal* / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases* / metabolism
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Anoctamin-1
  • Sirolimus