Jan 22, 2015

Endothelin-1 protects human melanocytes from UV-induced DNA damage by activating JNK and p38 signalling pathways

Experimental Dermatology
Anne M von KoschembahrZalfa A Abdel-Malek


Endothelin-1 is a paracrine factor with mitogenic, melanogenic and survival effects on cultured human melanocytes. We report that endothelin-1 signalling reduced the generation and enhanced the repair of ultraviolet radiation (UV)-induced DNA photoproducts, and inhibited apoptosis of human melanocytes, without increasing cAMP levels, melanin content or proliferation. Treatment with endothelin-1 activated the MAP kinases JNK and p38, as evidenced by phosphorylation of their target, activating transcription factor-2 (ATF-2). Endothelin-1 also enhanced the phosphorylation of JNK, p38 and ATF-2 by UV. The effects of endothelin-1 were dependent on increasing intracellular calcium mobilization by endothelin B receptor signalling. Activation of both JNK and p38 was required for reducing DNA photoproducts, but only JNK partially contributed to the survival effect of endothelin-1. ATF-2 activation depended mainly on JNK, yet was not sufficient for the effect of endothelin-1 on UV-induced DNA damage, suggesting the requirement for other JNK and p38 targets for this effect. Our results underscore the significance of endothelin-1 and endothelin B receptor signalling in reducing the genotoxic effects of UV via activating JNK and p38, hence ...Continue Reading

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Mentioned in this Paper

Activating Transcription Factors
Biochemical Pathway
Genomic Stability
Protein Phosphorylation
Paracrine Protein Factors
Receptor, Endothelin B, Type 2
Cyclic AMP

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis