High fatty acids modulate P2X7 expression and IL-6 release via the p38 MAPK pathway in PC12 cells

Hong Xu, Bing Wu, Fuqing Jiang, Shaoheng Xiong, Baoping Zhang, Guilin Li, Shuangmei Liu, Yun Gao, Changshui Xu, Guihua Tu, Haiying Peng, Shangdong Liang, Huangui Xiong

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Diabetic neuropathy (DNP) is the most common chronic complication of diabetes. Elevated free fatty acids (FFAs) have been recently recognized as a major cause of nervous system damage in diabetes. P2X receptors play a primary role in regulation of neuronal interleukin (IL)-6 release, which is of paramount relevance to the functional changes of nerve system. The present study aimed to investigate the effects of high FFAs on the P2X7 expression and IL-6 release in PC12 cells. High FFAs induced P2X7 expression and IL-6 release significantly in PC12 cells. Moreover, high FFAs enhanced ATP or BzATP-induced Ca2+ signals in PC12 cells. Inhibition of P2X7 by transfection with P2X7-siRNA or co-culture with BBG (a specific P2X7 inhibitor) at high concentrations of FFAs decreased ATP or BzATP-promoted Ca2+ signals and IL-6 release in PC12 cells. High FFAs induced the phosphorylation of p38 in PC12 cells. Blockade of p38 pathways by SB-203580 inhibited P2X7 up-expression, ATP or BzATP-evoked [Ca2+]i rises as well as IL-6 release in PC12 cells exposed to high FFAs. Therefore, high concentrations of FFAs increased the expression of P2X7 in PC12 cells via activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway, which contributed to P2X7-mediated IL-6 release from PC12 cells.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalBrain Research Bulletin
Volume94
DOIs
StatePublished - May 2013

Keywords

  • Diabetic neuropathy
  • High fatty acids
  • P2X7 receptor
  • P38
  • PC12

ASJC Scopus subject areas

  • Neuroscience(all)

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