Orexin-A promotes cell migration in cultured rat astrocytes via Ca2+-dependent PKCα and ERK1/2 signals

PLoS One. 2014 Apr 18;9(4):e95259. doi: 10.1371/journal.pone.0095259. eCollection 2014.

Abstract

Orexin-A is an important neuropeptide involved in the regulation of feeding, arousal, energy consuming, and reward seeking in the body. The effects of orexin-A have widely studied in neurons but not in astrocytes. Here, we report that OX1R and OX2R are expressed in cultured rat astrocytes. Orexin-A stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and then induced the migration of astrocytes via its receptor OX1R but not OX2R. Orexin-A-induced ERK1/2 phosphorylation and astrocytes migration are Ca2+-dependent, since they could be inhibited by either chelating the extracellular Ca2+ or blocking the pathway of store-operated calcium entry (SOCE). Furthermore, both non-selective protein kinase C (PKC) inhibitor and PKCα selective inhibitor, but not PKCδ inhibitor, prevented the increase in ERK1/2 phosphorylation and the migration of astrocytes, indicating that the Ca2+-dependent PKCα acts as the downstream of the OX1R activation and mediates the orexin-A-induced increase in ERK1/2 phosphorylation and cell migration. In conclusion, these results suggest that orexin-A can stimulate ERK1/2 phosphorylation and then facilitate the migration of astrocytes via PLC-PKCα signal pathway, providing new knowledge about the functions of the OX1R in astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / enzymology
  • Astrocytes / metabolism*
  • Calcium / metabolism*
  • Cell Movement / physiology*
  • Cells, Cultured
  • DNA Primers
  • Intracellular Signaling Peptides and Proteins / physiology*
  • MAP Kinase Signaling System*
  • Neuropeptides / physiology*
  • Orexins
  • Phosphorylation
  • Protein Kinase C-alpha / metabolism*
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Type C Phospholipases / metabolism

Substances

  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Protein Kinase C-alpha
  • Type C Phospholipases
  • Calcium

Grants and funding

This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2013CB531303) and the National Natural Science Foundation of China (NSFC, Key Project, No. 30930104) to Dr. J.G. Chen. It was also supported by NSFC grants to Dr. F. Wang (No. 81222048) and to Z.L. Hu (No. 81173071). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.