{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:24:45Z","timestamp":1785468285006,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T00:00:00Z","timestamp":1534723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Chi-Mei Medical Center","award":["CMFHT10503"],"award-info":[{"award-number":["CMFHT10503"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peroxisome proliferator\u2010activated receptor \u03b4 (PPAR\u03b4), the predominant PPAR subtype in the heart, is known to regulate cardiac function. PPAR\u03b4 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\u03b4. 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\u2010cells, were reduced by GW0742. This reduction was parallel to the decrease in the mRNA levels of biomarkers, such as brain\/B\u2010type natriuretic peptides and \u03b2\u2010myosin heavy chain. These effects of GW0742 were dose\u2010dependently inhibited by GSK0660 indicating an activation of PPAR\u03b4 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\u03b4 agonists can inhibit free radicals, resulting in lower cellular calcium for reduction of hypertrophic signaling to alleviate cardiac hypertrophy in H9c2 cells. Therefore, PPAR\u03b4 activation can be used to develop agent(s) for treating cardiac hypertrophy.<\/jats:p>","DOI":"10.1002\/jcb.27270","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:24:44Z","timestamp":1534951484000},"page":"9532-9542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["GW0742 activates peroxisome proliferator\u2010activated receptor \u03b4 to reduce free radicals and alleviate cardiac hypertrophy induced by hyperglycemia in cultured H9c2 cells"],"prefix":"10.1002","volume":"119","author":[{"given":"Kai\u2010Chun","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Psychosomatic Internal Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Internal Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"},{"name":"Department of Medical Research Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung\u2010Ze","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-584X","authenticated-orcid":false,"given":"Juei\u2010Tang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chi\u2010Mei Medical Center Tainan Taiwan"},{"name":"Graduate Institute of Medical Science, Chang Jung Christian University, Gueiren Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhih\u2010Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chi\u2010Mei Medical Center Tainan Taiwan"},{"name":"Department of Pharmacy Chia Nan University of Pharmacy &amp; Science Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jev155"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.04.005"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.679597"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.02.082"},{"key":"e_1_2_6_1_7_1","first-page":"411","article-title":"Diabetic cardiomyopathy: from pathophysiology to treatment","volume":"55","author":"Trachanas K","year":"2014","journal-title":"Hellenic J Cardiol"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-013-9381-z"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161025234"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12762"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000060700.55247.7C"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.11.011"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10641960801945840"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1116"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000459708"},{"key":"e_1_2_6_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0297-0"},{"key":"e_1_2_6_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.12.012"},{"key":"e_1_2_6_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmau.2015.03.003"},{"key":"e_1_2_6_1_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2002.1526"},{"key":"e_1_2_6_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.10.019"},{"key":"e_1_2_6_1_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01212.x"},{"key":"e_1_2_6_1_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071364"},{"key":"e_1_2_6_1_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-11-73"},{"key":"e_1_2_6_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.07.005"},{"key":"e_1_2_6_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.09.008"},{"key":"e_1_2_6_1_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-014-2120-5"},{"key":"e_1_2_6_1_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603770380034"},{"key":"e_1_2_6_1_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/461967"},{"key":"e_1_2_6_1_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-89"},{"key":"e_1_2_6_1_30_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v5.i6.164"},{"key":"e_1_2_6_1_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023116"},{"key":"e_1_2_6_1_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091958"},{"key":"e_1_2_6_1_33_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1253373"},{"key":"e_1_2_6_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00207-5"},{"key":"e_1_2_6_1_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0190"},{"key":"e_1_2_6_1_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(76)90447-X"},{"key":"e_1_2_6_1_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-010-9368-1"},{"key":"e_1_2_6_1_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1614"},{"key":"e_1_2_6_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.002"},{"key":"e_1_2_6_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.02.020"},{"key":"e_1_2_6_1_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp106"},{"key":"e_1_2_6_1_42_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v6.i8.744"},{"key":"e_1_2_6_1_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.222562"},{"key":"e_1_2_6_1_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206185"},{"key":"e_1_2_6_1_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000163846.51473.09"},{"key":"e_1_2_6_1_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.68.5.1390"},{"key":"e_1_2_6_1_47_1","first-page":"H823","article-title":"Free radicals enhance Na+\/Ca2+exchange in ventricular myocytes","volume":"271","author":"Goldhaber JI","year":"1996","journal-title":"Am J Physiol"},{"key":"e_1_2_6_1_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.194035"},{"key":"e_1_2_6_1_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12164"},{"key":"e_1_2_6_1_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(91)90330-9"},{"key":"e_1_2_6_1_51_1","first-page":"1379","article-title":"Preventive effect of vanillin on lipid peroxides and antioxidants in potassium bromate\u2010induced cardiotoxicity in adult mice: biochemical and histopathological evidences","volume":"6","author":"Hajer Ben Saad IK","year":"2017","journal-title":"Journal of Pharmacognosy and Phytochemistry"},{"key":"e_1_2_6_1_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22038"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.27270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.27270","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T15:57:38Z","timestamp":1744819058000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.27270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,20]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/jcb.27270"],"URL":"https:\/\/doi.org\/10.1002\/jcb.27270","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,20]]},"assertion":[{"value":"2018-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}