GW0742 activates peroxisome proliferator-activated receptor delta to reduce free radicals and alleviate cardiac hypertrophy induced by hyperglycemia in cultured H9c2 cells

doi:10.1002/jcb.27270

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Title:	GW0742 activates peroxisome proliferator-activated receptor delta to reduce free radicals and alleviate cardiac hypertrophy induced by hyperglycemia in cultured H9c2 cells
Authors:	Cheng, Kai-Chun Chang, Wei-Ting Li, Yingxiao Cheng, Yung-Ze Cheng, Juei-Tang Chen, Zhih-Cherng
Contributors:	Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med Chi Mei Med Ctr, Dept Cardiol Chi Mei Med Ctr, Dept Med Res Chi Mei Med Ctr, Dept Emergency Med Chang Jung Christian Univ, Grad Inst Med Sci Chia Nan Univ Pharm & Sci, Dept Pharm
Keywords:	cardiac hypertrophy GSK0660 GW0742 H9c2 cells peroxisome proliferator-activated receptor (PPAR)
Date:	2018-11
Issue Date:	2019-11-15 15:48:31 (UTC+8)
Publisher:	WILEY
Abstract:	Peroxisome proliferator-activated receptor (PPAR), the predominant PPAR subtype in the heart, is known to regulate cardiac function. PPAR activation may inhibit cardiac hypertrophy in H9c2 cells while the potential mechanism has not been elucidated. Then, H9c2 cells incubated with high glucose to induce hypertrophy were used to investigate using GW0742 to activate PPAR. The fluorescence assays were applied to determine the changes in cell size, cellular calcium levels, and free radicals. Western blot analyses for hypertrophic signals and assays of messenger RNA (mRNA) levels for hypertrophic biomarkers were performed. In H9c2 cells, GW0742 inhibited cardiac hypertrophy. In addition, increases in cellular calcium and hypertrophic signals, including calcineurin and nuclear factor of activated T-cells, were reduced by GW0742. This reduction was parallel to the decrease in the mRNA levels of biomarkers, such as brain/B-type natriuretic peptides and -myosin heavy chain. These effects of GW0742 were dose-dependently inhibited by GSK0660 indicating an activation of PPAR by GW0742 to alleviate cardiac hypertrophy. Moreover, free radicals produced by hyperglycemia were also markedly inhibited by GW0742 and were later reversed by GSK0660. GW0742 promoted the expression of thioredoxin, an antioxidant enzyme. Direct inhibition of reactive oxygen species by GW0742 was also identified in the oxidant potassium bromate stimulated H9c2 cells. Taken together, these findings suggest that PPAR agonists can inhibit free radicals, resulting in lower cellular calcium for reduction of hypertrophic signaling to alleviate cardiac hypertrophy in H9c2 cells. Therefore, PPAR activation can be used to develop agent(s) for treating cardiac hypertrophy.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.1002/jcb.27270
Relation:	Journal of Applied Polymer Science, v.119, n.11, pp.9532-9542
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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