The microphthalmia-associated transcription factor Mitf plays a critical role in regulating many aspects of melanocyte biology. It is required for melanoblast and postnatal melanocyte survival, regulates proliferation, and activates genes associated with differentiation such as tyrosinase and related genes involved in melanogenesis. Identifying the signals that regulate Mitf expression is crucial if we are to understand how cells of the melanocyte lineage respond to environmental cues. Here we show that the Mitf promoter is induced by lipid signalling via the p38 stress-activated kinase pathway that is also activated by a wide range of receptors as well as UV irradiation. Signalling via p38 leads to increased phosphorylation and activation of cyclic adenosine monophosphate response element-binding (CREB) that binds and activates the Mitf promoter via the cyclic adenosine monophosphate (cAMP) response element. Moreover, we also show that activation of p38 mediated by lipids is potentiated by inhibition of the PI3kinase pathway but not by inhibition of protein kinase A (PKA). The results identify a mechanism in which stress signalling via p38 leads to activation of CREB, enhanced Mitf expression and consequently increased tyrosinase expression. The results are relevant for the regulation of melanocytes by Mitf, but also raise the possibility that lipid mediated activation of p38 signalling may represent a potential therapy for vitiligo.

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Zinc ion fluorescence sensing and the binding properties of 4-methyl-2,6-bis(((phenylmethyl)imino)methyl)phenol (HL) have been investigated. It displays high selectivity for Zn2+ and can be used as zinc ion-selective luminescent probe for biological application under physiological conditions. The increase in emission in the presence of Zn2+ is accounted for by the formation of hexanuclear complex [Zn6(L)2(OH)2(CH3COO)8] characterized by X-ray crystallography. An approximately 6-fold Zn2+-selective chelation-enhanced fluorescence response in HEPES buffer (pH 7.4) is attributed due to the strong coordination of Zn(II) that would impose rigidity and hence decrease the nonradiative decay of the excited state. By incubation of cultured living cells (B16F10 mouse melanoma and A375 human melanoma) with HL, intracellular Zn2+ concentration could be monitored.