Downregulation of TRPM7, TRPM8, and TRPV1 channels modulate apoptotic parameters and neurodegenerative markers: Focus on neuronal differentiation and Parkinson's disease model

Cell Biol Int. 2023 Sep;47(9):1502-1518. doi: 10.1002/cbin.12048. Epub 2023 May 19.

Abstract

The transient receptor potential channel (TRP) channels are expressed in neuronal tissues and involved in neurological diseases such as pain, epilepsy, neuronal apoptosis, and neurodegenerative diseases. Formerly, we have investigated how neuronal differentiation changes TRP channels expression profile and how Parkinson's disease model is related with this expression levels. We have found that transient receptor potential channel melastatin subtype 7 (TRPM7), transient receptor potential channel melastatin subtype 8 and transient receptor potential channel vanilloid subtype 1 (TRPV1) channels have pivotal effects on differentiation and 1-Methyl-4-phenylpyridinium (MPP+ )-induced Parkinson's disease model in SH-SY5Y cells. In this study, we have investigated that downregulation of the TRP channels to evaluate how differentiation status changes to Parkinson's disease pathological hallmarks. We have also performed to other analyses to elucidate these TRP channels' function in MPP+ -induced neurotoxicity related apoptosis, cell viability, caspase 3 and 9 enzyme activities, intracellular reactive oxygen species production, mitochondrial depolarization levels, Ca2+ signaling, Alpha-synuclein and Dopamine levels, mono amino oxidase A and B enzymatic activities, both in differentiated and undifferentiated neuronal cells. Herein we have concluded that especially TRPM7 and TRPV1 channels have distinct role in Parkinson's disease pathology via their activity changings in pathological state, and downregulation of these channels or specific antagonists can be useful for the possible treatment strategy for Parkinson's disease and related markers.

Keywords: Parkinson's disease; TRPM7 channels; TRPM8 channels; TRPV1 channels; neuronal differentiation.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology
  • Apoptosis
  • Down-Regulation
  • Humans
  • Membrane Proteins / metabolism
  • Neuroblastoma*
  • Parkinson Disease*
  • Protein Serine-Threonine Kinases / metabolism
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels* / metabolism

Substances

  • Transient Receptor Potential Channels
  • TRPM Cation Channels
  • 1-Methyl-4-phenylpyridinium
  • TRPV1 protein, human
  • TRPV Cation Channels
  • TRPM7 protein, human
  • Protein Serine-Threonine Kinases
  • TRPM8 protein, human
  • TRPM8 channel-associated factor 1 protein, human
  • Membrane Proteins