TRPV1-dependent ERK1/2 activation in porcine lens epithelium

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Recently we determined that the Transient Receptor Potential Vanilloid 4 ion channel (TRPV4) has a crucial signaling role in a pathway that regulates various aspects of lens epithelium function. Here, we report on a different TRPV channel, TRPV1, in porcine lens. The presence of TRPV1 in the lens was evident from RT-PCR studies and Western blot analysis of MAPK signaling pathway activation caused by the TRPV1 agonist capsaicin. TRPV1 mRNA was detected in the epithelium of porcine as well as human lens. Transient ERK1/2 and p38 MAPK phosphorylation was detected within 1 min in the epithelium isolated from intact porcine lenses exposed to capsaicin (100 nM), a selective TRPV1 agonist, and the response was significantly inhibited by A889245 (1.0 μM), a TRPV1 antagonist. A similar ERK 1/2 and p38 response in the epithelium, also inhibitable by A889245, was evident in lenses treated with hyperosmotic solution (350 vs 300 mOsm). Lenses pre-treated with either the cytosolic Ca2+ chelator BAPTA-AM or the PKC inhibitor sotrastaurin (1.0 μM) had a diminished ERK1/2 activation response to capsaicin and hyperosmotic solution. Taken together the findings support the notion that TRPV1 functions as a plasma membrane ion channel that, when activated, permits the entry of extracellular calcium into the lens epithelium, leading to activation of PKC, ERK1/2 and p38 MAPK. It is significant that the findings confirm earlier proposals that hyperosmotic stress is linked to TRPV1 channel activation in the mouse lens. Further studies are ongoing to determine what functional changes are triggered by the TRPV1-linked signaling pathways and how they might relate to lens volume homeostasis.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalExperimental eye research
Volume172
DOIs
StatePublished - Jul 2018

Keywords

  • ERK1/2
  • Lens epithelium
  • P38 MAPK
  • TRPV1

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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