TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization

Biochem Biophys Res Commun. 2008 May 16;369(4):989-93. doi: 10.1016/j.bbrc.2008.02.155. Epub 2008 Mar 10.

Abstract

Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca(2+)](c)) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca(2+)](c) and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca(2+)](c) elevation, ROS production, and mitochondrial membrane depolarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Calcium / metabolism*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Cytosol / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Hyperplasia
  • Male
  • Membrane Potential, Mitochondrial
  • NADPH Oxidases / antagonists & inhibitors
  • Onium Compounds / pharmacology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*

Substances

  • Onium Compounds
  • Reactive Oxygen Species
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • diphenyleneiodonium
  • NADPH Oxidases
  • capsazepine
  • Capsaicin
  • Calcium