title: High fatty acids modulate P2X(7) expression and IL-6 release via the p38 MAPK pathway in PC12 cells.
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 Ca(2+) 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 Ca(2+) 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 [Ca(2+)]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.
authors: Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China.
authors: Hong
authors: H
authors: Xu
authors: Bing
authors: B
authors: Wu
authors: Fuqing
authors: F
authors: Jiang
authors: Shaoheng
authors: S
authors: Xiong
authors: Baoping
authors: B
authors: Zhang
authors: Guilin
authors: G
authors: Li
authors: Shuangmei
authors: S
authors: Liu
authors: Yun
authors: Y
authors: Gao
authors: Changshui
authors: C
authors: Xu
authors: Guihua
authors: G
authors: Tu
authors: Haiying
authors: H
authors: Peng
authors: Shangdong
authors: S
authors: Liang
authors: Huangui
authors: H
authors: Xiong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016716:PC12 Cells; D034741:RNA, Small Interfering; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D005227:Fatty Acids; D015850:Interleukin-6; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7