ORAI1 Ca2+ Channels Control Endothelin-1-Induced Mitogenesis and Melanogenesis in Primary Human Melanocytes

Stanisz, Hedwig and Stark, Alexandra and Kilch, Tatiana and Schwarz, Eva C and Müller, Cornelia S L and Peinelt, Christine and Hoth, Markus and Niemeyer, Barbara A. and Vogt, Thomas and Bogeski, Ivan (2012) ORAI1 Ca2+ Channels Control Endothelin-1-Induced Mitogenesis and Melanogenesis in Primary Human Melanocytes. Journal of Investigative Dermatology, 132 (5). pp. 1443-1451. ISSN 0022-202X

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Official URL: http://dx.doi.org/10.1038/jid.2011.478

Abstract

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 Ca2þ
concentration ([Ca2þ]i), which is necessary for proliferation and melanogenesis. A major fraction of the
Ca2þ signal is caused by entry through Ca2þ-permeable channels of unknown identity in the plasma
membrane. ORAI Ca2þ channels are molecular determinants of Ca2þ release-activated Ca2þ (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 Ca2þ 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:	Article
Subjects:	Medical and Health Sciences > Basic medicine Medical and Health Sciences > Clinical medicine Medical and Health Sciences > Health sciences
Divisions:	Faculty of Medical Science
Depositing User:	Ivan Bogeski
Date Deposited:	27 Nov 2012 10:46
Last Modified:	24 Apr 2013 10:46
URI:	https://eprints.ugd.edu.mk/id/eprint/2207

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