We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
ORAI1 Ca<sup>2+</sup> Channels Control Endothelin-1-Induced Mitogenesis and Melanogenesis in Primary Human Melanocytes.
- Authors
Stanisz, Hedwig; Stark, Alexandra; Kilch, Tatiana; Schwarz, Eva C; Müller, Cornelia S L; Peinelt, Christine; Hoth, Markus; Niemeyer, Barbara A; Vogt, Thomas; Bogeski, Ivan
- 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 Ca2+ concentration ([Ca2+]i), which is necessary for proliferation and melanogenesis. A major fraction of the Ca2+ signal is caused by entry through Ca2+-permeable channels of unknown identity in the plasma membrane. ORAI Ca2+ channels are molecular determinants of Ca2+ release-activated Ca2+ (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 Ca2+ 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.
- Subjects
MELANOCYTES; MELANOGENESIS; KERATINOCYTES; ENDOTHELINS; ULTRAVIOLET radiation
- Publication
Journal of Investigative Dermatology, 2012, Vol 132, Issue 5, p1443
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2011.478