Oral communication, iL25

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Modulatory effects of a small peptide derivative of alpha-MSH, KdPT, on melanocyte responses to oxidative stress

It is well known that alpha-MSH has pigment-inducing and cytoprotective effects in human melanocytes. This natural peptide has also an ever increasing number of anti-inflammatory properties that may be useful for the treatment of immune-mediated inflammatory diseases. However, topical therapy with such a peptide has never been realized in routine dermatology. We have thus started to explore the functional properties of Lys-d-Pro-Thr (KdPT), a tripeptide derivative of the C-terminal domain of alpha-MSH. This small peptide has a MW of <400 Da and may thus be suitable for topical therapy in dermatology. We could recently demonstrate that KdPT neither binds to Mc1r expressing B16.F1 melanoma cells nor affects melanogenesis in these cells as well as in normal human melanocytes. Since KdPT reduces IL-1beta-induced signaling, accumulation of reactive oxygen species and proinflammatory cytokine expression in non-melanocytic cells, we wondered if this agent has any salutary effects in normal human melanocytes. Using 4-tertiary butyl phenol (4-TBP) as an established pro-oxidative cellular stressor we could demonstrate that 4-TBP-induced apoptosis is dose-dependently reduced by KdPT. Interestingly, KdPT per se moderately but significantly increased the expression of the transcription factor nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) at mRNA and protein level pointing towards an indirect antioxidative effect of the peptide. Interestingly, when normal human melanocytes were preincubated with KdPT, 4-TBP-induced expression of Nrf2 and nrf2-dependent genes (HO-1, gamma-GCS, GSTPi and NQO1) was significantly attenuated. In summary, our findings provide first evidence for a modulatory effect of KdPT in normal human melanocytes. The data further demonstrate that this small peptide has some protective effects against 4-TBP-induced apoptosis presumably by modulating the phase II detoxification enzymatic machinery. It will be very interesting to further assess the protective role of KdPT in adequate in vivo models of vitiligo.

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