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

doi:10.1016/j.brainresbull.2013.02.002

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 journal › Article › peer-review

32 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 language	English (US)
Pages (from-to)	63-70
Number of pages	8
Journal	Brain Research Bulletin
Volume	94
DOIs	https://doi.org/10.1016/j.brainresbull.2013.02.002
State	Published - May 2013
Externally published	Yes

Keywords

Diabetic neuropathy
High fatty acids
P2X7 receptor
P38
PC12

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.brainresbull.2013.02.002

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@article{c6ddffcf65444c91b3bb87b6a3addad9,

title = "High fatty acids modulate P2X7 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 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.",

keywords = "Diabetic neuropathy, High fatty acids, P2X7 receptor, P38, PC12",

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

note = "Funding Information: This work was supported by the grants (nos. 81171184 , 31060139 , 30860086 , 30660048 , 81100829 , 81260187 and 81200853 ) from National Natural Science Foundation of China , the grants (nos. 0640042 and 2008GZY0029 ) from Natural Science Foundation of Jiangxi Province , the grant (nos. 2010BSA09500 and 20111BBG70009-1 ) from Technology Pedestal and Society Development Project of Jiangxi Province , the grant (no. GJJ12149 ) from Young Foundation of the Education Department of Jiangxi Province , and the grant (no. 20122BAB215005 ) from Young Foundation of Jiangxi Province .",

year = "2013",

month = may,

doi = "10.1016/j.brainresbull.2013.02.002",

language = "English (US)",

volume = "94",

pages = "63--70",

journal = "Brain Research Bulletin",

issn = "0361-9230",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - High fatty acids modulate P2X7 expression and IL-6 release via the p38 MAPK pathway in PC12 cells

AU - Xu, Hong

AU - Wu, Bing

AU - Jiang, Fuqing

AU - Xiong, Shaoheng

AU - Zhang, Baoping

AU - Li, Guilin

AU - Liu, Shuangmei

AU - Gao, Yun

AU - Xu, Changshui

AU - Tu, Guihua

AU - Peng, Haiying

AU - Liang, Shangdong

AU - Xiong, Huangui

N1 - Funding Information: This work was supported by the grants (nos. 81171184 , 31060139 , 30860086 , 30660048 , 81100829 , 81260187 and 81200853 ) from National Natural Science Foundation of China , the grants (nos. 0640042 and 2008GZY0029 ) from Natural Science Foundation of Jiangxi Province , the grant (nos. 2010BSA09500 and 20111BBG70009-1 ) from Technology Pedestal and Society Development Project of Jiangxi Province , the grant (no. GJJ12149 ) from Young Foundation of the Education Department of Jiangxi Province , and the grant (no. 20122BAB215005 ) from Young Foundation of Jiangxi Province .

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Diabetic neuropathy

KW - High fatty acids

KW - P2X7 receptor

KW - P38

KW - PC12

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U2 - 10.1016/j.brainresbull.2013.02.002

DO - 10.1016/j.brainresbull.2013.02.002

M3 - Article

C2 - 23438872

AN - SCOPUS:84875620255

SN - 0361-9230

VL - 94

SP - 63

EP - 70

JO - Brain Research Bulletin

JF - Brain Research Bulletin

ER -

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

Abstract

Keywords

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