Interaction between necroptosis and p38MAPK pathway mediates high glucose-induced injury in H9 c2 cardiac cells
10.3969/j.issn.1001-1978.2016.08.021
- VernacularTitle:坏死性凋亡和 p38 MAPK 通路的相互作用介导高糖引起的 H9 c2心肌细胞损伤
- Author:
Weijie LIANG
;
Jieyi HE
;
Jun CHEN
;
Shenglong YU
;
Wenzhu ZHANG
;
Mingcai SONG
;
Jingfu CHEN
;
Jianqiang FENG
;
Xinxue LIAO
- Publication Type:Journal Article
- Keywords:
necroptosis;
p38 mitogen-activated protein kinase;
interaction;
high glucose;
cardiomyocyte;
in-jury
- From:
Chinese Pharmacological Bulletin
2016;32(8):1138-1143,1144
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the role of the interac-tion between necroptosis ( Nec ) and p38 mitogen-acti-vated protein kinase ( MAPK) pathway in the high glu-cose (HG)-induced H9c2 cardiac cells injury.Meth-ods The cell viability was measured by cell counter kit-8 assay .The intracellular level of reactive oxygen species ( ROS ) was tested by DCFH-DA stating fol-lowed by photofluorography .Mitochondrial membrane potential ( MMP) was detected by Rhodamine 123 stai-ning followed by photofluorography . The expression levels of receptor interaction protein 3 ( RIP3, an indi-cator of Nec ) and p38 MAPK protein were tested by Western blot assay .Results The treatment of H9c2 cardiac cells with 35 mmol? L-1 glucose ( high glu-cose, HG) for 24 h induced considerable injuries , in-cluding a decrease in cell viability , increases in ROS generation as well as MMP loss .The co-treatment of the cells with 100 μmol? L-1 necrostatin-1(Nec-1,a specific inhibitor of Nec ) and HG for 24 h or the pre-treatment of the cells with 3 μmol? L-1 SB 2 0 3 5 8 0 ( an inhibitor of p38MAPK) for 60 min before HG exposure attenuated the above injuries induced by HG .Moreo-ver, the treatment of the cells with HG for 1,3,6,9, 12 ,24 ,36 and 48 h significantly increased the expres-sion levels of RIP3, peaking at 24 h.The co-treatment of the cells with 100 μmol? L-1 Nec-1 or the pre-treatment of the cells with 3 μmol? L-1 SB203580 considerably blocked the up-regulation of RIP3 expres-sion induced by HG .On the other hand , the co-treat-ment of the cells with 100 μmol? L-1 Nec-1 alleviated the HG-induced up-regulation of the expression of p-p38MAPK.Conclusion The interaction between Nec and p38 MAPK pathway mediates the HG-induced inju-ry in H9c2 cardiac cells.
