ORAI1 Ca(2+) channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes.

Stanisz, Hedwig; Stark, Alexandra; Kilch, Tatiana; Schwarz, Eva C; Müller, Cornelia S L; Peinelt, Christine; Hoth, Markus; Niemeyer, Barbara A; Vogt, Thomas; Bogeski, Ivan (2012). ORAI1 Ca(2+) channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes. Journal of Investigative Dermatology, 132(5), pp. 1443-1451. Nature Publishing 10.1038/jid.2011.478

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UV radiation of the skin triggers keratinocytes to secrete endothelin-1 (ET-1) that binds to endothelin receptors on neighboring melanocytes. Melanocytes respond with a prolonged increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), which is necessary for proliferation and melanogenesis. A major fraction of the Ca(2+) signal is caused by entry through Ca(2+)-permeable channels of unknown identity in the plasma membrane. ORAI Ca(2+) channels are molecular determinants of Ca(2+) release-activated Ca(2+) (CRAC) channels and are expressed in many tissues. Here, we show that ORAI1-3 and their activating partners stromal interaction molecules 1 and 2 (STIM1 and STIM2) are expressed in human melanocytes. Although ORAI1 is the predominant ORAI isoform, STIM2 mRNA expression exceeds STIM1. Inhibition of ORAI1 by 2-aminoethoxydiphenyl borate (2-APB) or downregulation of ORAI1 by small interfering RNA (siRNA) reduced Ca(2+) entry and CRAC current amplitudes in activated melanocytes. In addition, suppression of ORAI1 caused reduction in the ET-1-induced cellular viability, melanin synthesis, and tyrosinase activity. Our results imply a role for ORAI1 channels in skin pigmentation and their potential involvement in UV-induced stress responses of the human skin.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Peinelt, Christine

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-202X

Publisher:

Nature Publishing

Language:

English

Submitter:

Christine Peinelt

Date Deposited:

19 Jun 2018 11:49

Last Modified:

05 Dec 2022 15:03

Publisher DOI:

10.1038/jid.2011.478

PubMed ID:

22318387

BORIS DOI:

10.7892/boris.97457

URI:

https://boris.unibe.ch/id/eprint/97457

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