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As a key regulator of melanogenesis, p53 controls microphthalmia-associated transcriptionfactor (MITF) and tyrosinase expression. The anti-oxidant enzyme heme oxygenase-1 (HO-1) is induced by various forms of cellular stress and diverse oxidativestimuli. However, few studies have examined the role of HO-1 in melanogenesis. Therefore, the aim of this study was to determine the role of HO-1 in melanogenesisand the mechanism underlying this relationship. Cultures of normal human melanocyteswere treated with the HO-1 inducer cobalt protoporphyrin (CoPP) or the HO-1inhibitor zinc protoporphyrin (ZnPP). We then measured the melanin content of thecells. Additional analyses consisted of Western blotting and RT-PCR. The resultsshowed that the cellular melanin content was increased by CoPP and decreased byZnPP. The Western blot and RT-PCR analyses showed that CoPP increased p53, MITFand tyrosinase levels, and ZnPP reduced all of them. The knockdown of p53 by siRNAtransfection was followed by large decreases in the expression levels of p53, MITF andtyrosinase at 3 h of transfection. The presence of CoPP or ZnPP had no significant increasedor decreased effects on MITF and tyrosinase levels from 15 h in the siRNAtransfectants. Our results suggest that HO-1 modulates melanogenesis in human melanocytesvia a p53-dependent pathway.
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참고문헌 (14)
참고문헌 신청
Amersi F / 1999 / Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury / J Clin Invest 104:1631~1639
Schallreuter KU / 2008 / Regulation of melanogenesis--controversies and new concepts / Exp Dermatol 17:395~404
Zhao H / 2015 / Heme oxygenase-1 in pregnancy and cancer: similarities in cellular invasion, cytoprotection, angiogenesis, and immunomodulation / Front Pharmacol 5:295
Jian Z / 2011 / Heme oxygenase-1protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway / J Invest Dermatol 131:1420~1427
Jin SA / 2010 / Decreased heme oxygenase-1 expression distinguishes human melanomas from melanocytic nevi / Pigment Cell Melanoma Res 23:841~844
Schallreuter KU / 2008 / Regulation of melanogenesis--controversies and new concepts / Exp Dermatol 17:395~404
Zhao H / 2015 / Heme oxygenase-1 in pregnancy and cancer: similarities in cellular invasion, cytoprotection, angiogenesis, and immunomodulation / Front Pharmacol 5:295
Jian Z / 2011 / Heme oxygenase-1protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway / J Invest Dermatol 131:1420~1427
Jin SA / 2010 / Decreased heme oxygenase-1 expression distinguishes human melanomas from melanocytic nevi / Pigment Cell Melanoma Res 23:841~844
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