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Opsin3 Downregulation Induces Apoptosis of Human Epidermal Melanocytes via Mitochondrial Pathway
Author(s) -
Wang Yu,
Lan Yinghua,
Lu Hongguang
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13178
Subject(s) - microbiology and biotechnology , apoptosome , downregulation and upregulation , biology , apoptosis , mitochondrion , caspase , cytochrome c , signal transduction , phosphorylation , programmed cell death , calcium signaling , biochemistry , gene
G protein‐coupled receptors (GPCRs) are core switches connecting excellular survival or death signals with cellular signaling pathways in a context‐dependent manner. Opsin 3 (OPN3) belongs to the GPCR superfamily. However, whether OPN3 can control the survival or death of human melanocytes is not known. Here, we try to investigate the inherent function of OPN3 on the survival of melanocytes. Our results demonstrate that OPN3 knockdown by RNAi‐OPN3 in human epidermal melanocytes leads to cell apoptosis. The downregulation of OPN3 markedly reduces intracellular calcium levels and decreases phosphorylation of BAD. Attenuated BAD phosphorylation and elevated BAD protein level alter mitochondria membrane permeability, which trigger activation of BAX and inhibition of BCL‐2 and raf‐1. Activated BAX results in the release of cytochrome c and the loss of mitochondrial membrane potential. Cytochrome c complexes associate with caspase 9, forming a postmitochondrial apoptosome that activate effector caspases including caspase 3 and caspase 7. The release of apoptotic molecules eventually promotes the occurrence of apoptosis. In conclusion, we hereby are the first to prove that OPN3 is a key signal responsible for cell survival through a calcium‐dependent G protein‐coupled signaling and mitochondrial pathway.