Methylglyoxal activates the human transient receptor potential ankyrin 1 channel

J Toxicol Sci. 2012;37(4):831-5. doi: 10.2131/jts.37.831.

Abstract

Methylglyoxal (MG) is an endogenous carbonyl compound that is produced in large quantity under hyperglycemic conditions, which are believed to contribute to the development of diabetic neuropathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. In the present study, we investigated the effect of MG on transient receptor potential ankyrin 1 (TRPA1) activation in human TRPA1-expressing HEK293 cells. MG activated TRPA1-expressing HEK293 cells, but failed to activate human capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells or mock-transfected HEK293 cells. MG also induced calcium (Ca(2+)) influx in a concentration-dependent manner, and the concentration-response curve indicates that the effect of MG has an EC(50) of 343.1 ± 17.3 µM. Interestingly, the time course in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in human TRPA1-expressing HEK293 showed considerable differences in response to MG and cinnamaldehyde. Furthermore, we examined four endogenous carbonyl compounds, including MG, glyceraldehyde, glycolaldehyde, and glyoxal; only MG notably activated TRPA1-expressing HEK293 cells. These results may provide insight into the TRPA1-mediated effects of MG on diabetic neuropathy.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / analogs & derivatives
  • Acrolein / pharmacology
  • Calcium / analysis
  • Calcium / metabolism
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Capsaicin / pharmacology
  • Cloning, Molecular
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / pathology
  • HEK293 Cells
  • Humans
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / metabolism*
  • Pyruvaldehyde / pharmacology*
  • TRPA1 Cation Channel
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / agonists*
  • Transient Receptor Potential Channels / metabolism*

Substances

  • Calcium Channels
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • Pyruvaldehyde
  • Acrolein
  • Capsaicin
  • cinnamic aldehyde
  • Calcium