alpha-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines

We have previously shown that or-melanocyte-stimulating hormone (alpha-MSH) can oppose tumor necrosis factor (alpha activation of NF-KB (1-2 h) and in tercellular adhesion molecule 1 up-regulation (mRNA by 3 h and protein by 2 4 h) in melanocytes and melanoma cells. The present study reports on the ab ility of four MSH peptides to control intracellular peroxide levels and glu tathione peroxidase (GPx) activity in pigmentary and nonpigmentary cells. I n human HBL melanoma and HaCaT keratinocytes tumor necrosis factor alpha an d H2O2 both activated GPx in a time- and concentration-dependent manner (by 30-45 min). (alpha-MSH peptides were found to inhibit the stimulated GPx a ctivity and had biphasic dose-response curves. MSH 1-13 and MSH [Nle(4)-D-P he(7)] achieved maximum inhibition at 10(-10) and 10(-12) M, respectively. Higher concentrations (10-100 fold) of MSH 4-10 and MSH. 11-13 were require d to produce equivalent levels of inhibition. alpha-MSH was also capable of reducing peroxide accumulation within 15 min, and again this inhibition wa s biphasic. The data support a role of (alpha-MSH in acute protection of ce lls to oxidative/cytokine action that precedes NF-kappa B and GPx activatio n. The rapidity and potency of the response to alpha-MSH in pigmentary and nonpigmentary cells suggest this to be a central role of this peptide in cu taneous cells.