Chonnam Med J.  2016 Jan;52(1):45-52. 10.4068/cmj.2016.52.1.45.

Modulation of Melanogenesis by Heme Oxygenase-1 via p53 in Normal Human Melanocytes

Affiliations
  • 1Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea. sjyun@chonnam.ac.kr

Abstract

As a key regulator of melanogenesis, p53 controls microphthalmia-associated transcription factor (MITF) and tyrosinase expression. The anti-oxidant enzyme heme oxygenase-1 (HO-1) is induced by various forms of cellular stress and diverse oxidative stimuli. 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 melanogenesis and the mechanism underlying this relationship. Cultures of normal human melanocytes were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) or the HO-1 inhibitor zinc protoporphyrin (ZnPP). We then measured the melanin content of the cells. Additional analyses consisted of Western blotting and RT-PCR. The results showed that the cellular melanin content was increased by CoPP and decreased by ZnPP. The Western blot and RT-PCR analyses showed that CoPP increased p53, MITF and tyrosinase levels, and ZnPP reduced all of them. The knockdown of p53 by siRNA transfection was followed by large decreases in the expression levels of p53, MITF and tyrosinase at 3 h of transfection. The presence of CoPP or ZnPP had no significant increased or decreased effects on MITF and tyrosinase levels from 15 h in the siRNA transfectants. Our results suggest that HO-1 modulates melanogenesis in human melanocytes via a p53-dependent pathway.

Keyword

Heme oxygenase-1; Melanocytes; Melanins; Cobaltiprotoporphyrin; Zinc protoporphyrin

MeSH Terms

Blotting, Western
Cobalt
Heme Oxygenase-1*
Heme*
Humans*
Melanins
Melanocytes*
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase
RNA, Small Interfering
Transfection
Zinc
Cobalt
Heme
Heme Oxygenase-1
Melanins
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase
RNA, Small Interfering
Zinc
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