{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:58:48Z","timestamp":1788872328376,"version":"build-2803163510"},"reference-count":37,"publisher":"American Physiological Society","issue":"8","funder":[{"name":"The Major International (Regional) Joint Research Project","award":["2008DFA31140"],"award-info":[{"award-number":["2008DFA31140"]}]},{"name":"Chinese Science and Technology Support Program","award":["2011BAI11B22"],"award-info":[{"award-number":["2011BAI11B22"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81370230"],"award-info":[{"award-number":["81370230"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Sciences Foundation of Guangdong Province","award":["S2013010014009"],"award-info":[{"award-number":["S2013010014009"]}]},{"name":"The Major International (Regional) Joint Resaerch Project","award":["2010DFA32660"],"award-info":[{"award-number":["2010DFA32660"]}]},{"DOI":"10.13039\/501100004761","name":"Natural Sciences Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2015JJ6118"],"award-info":[{"award-number":["2015JJ6118"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Techology Foundation for Selected Overseas Chinese Scholar"},{"name":"Ministry of Hunan resources and Social Security od China (ZP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2015,4,15]]},"abstract":"<jats:p>\n                    Hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) causes cell damage via oxidative stress. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) could protect cardiomyocytes from H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced hypertrophy via modulation of HO-1 expression. HL-1 cells pretreated with\/without 5-ALA and SFC were exposed to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry,\n                    <jats:sup>3<\/jats:sup>\n                    H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species (ROS) production was assessed by 5\/6-chloromethyl-2\u2032,7\u2032-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. We found several results. 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and \u03b2-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and time-dependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1\/2, p38, and SAPK\/JNK signaling pathways were activated and modulate 5-ALA- and SFC-enhanced HO-1 expression. SB203580 (p38 kinase), PD98059 (ERK), or SP600125 (JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced cardiac hypertrophy via activation of the MAPK\/Nrf2\/HO-1 signaling pathway.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00369.2014","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:41:53Z","timestamp":1423096913000},"page":"C665-C672","source":"Crossref","is-referenced-by-count":34,"title":["5-Aminolevulinic acid combined with sodium ferrous citrate ameliorates H\n                    <sub>2<\/sub>\n                    O\n                    <sub>2<\/sub>\n                    -induced cardiomyocyte hypertrophy via activation of the MAPK\/Nrf2\/HO-1 pathway"],"prefix":"10.1152","volume":"308","author":[{"given":"Mingyi","family":"Zhao","sequence":"first","affiliation":[{"name":"Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;"},{"name":"Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimei","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Fujino","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan;"},{"name":"AIDS 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