Suppression of melanin production by expression of HSP70

Tatsuya Hoshino, Minoru Matsuda, Yasuhiro Yamashita, Masaya Takehara, Masayo Fukuya, Kazutaka Mineda, Daisuke Maji, Hironobu Ihn, Hiroaki Adachi, Gen Sobue, Yoko Funasaka, Tohru Mizushima

研究成果: Article査読

33 被引用数 (Scopus)

抄録

Skin hyperpigmentation disorders due to abnormal melanin production induced by ultraviolet (UV) irradiation are both a clinical and cosmetic problem. UV irradiation stimulates melanin production in melanocytes by increasing intracellular cAMP. Expression of heat shock proteins (HSPs), especially HSP70, is induced by various stressors, including UV irradiation, to provide cellular resistance to such stressors. In this study we examined the effect of expression of HSP70 on melanin production both in vitro and in vivo. 3-Isobutyl-1- methylxanthine (IBMX), a cAMP-elevating agent, stimulated melanin production in cultured mouse melanoma cells, and this stimulation was suppressed in cells overexpressing HSP70. IBMX-dependent transcriptional activation of the tyrosinase gene was also suppressed in HSP70-overexpressing cells. Expression of microphthalmia-associated transcription factor (MITF), which positively regulates transcription of the tyrosinase gene, was up-regulated by IBMX; however, this up-regulation was not suppressed in HSP70-overexpressing cells. On the other hand, immunoprecipitation and immunostaining analyses revealed a physical interaction between and co-localization of MITF and HSP70, respectively. Furthermore, the transcription of tyrosinase gene in nuclear extract was inhibited by HSP70. In vivo, UV irradiation of wild-type mice increased the amount of melanin in the basal layer of the epidermis, and this increase was suppressed in transgenic mice expressing HSP70. This study provides the first evidence of an inhibitory effect of HSP70 on melanin production both in vitro and in vivo. This effect seems to be mediated by modulation of MITF activity through a direct interaction between HSP70 and MITF.

本文言語English
ページ(範囲)13254-13263
ページ数10
ジャーナルJournal of Biological Chemistry
285
17
DOI
出版ステータスPublished - 2010 4 23

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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