Non-lesional vitiliginous melanocytes are not characterized by an increased proneness to nitric oxide-induced apoptosis

: Nitric oxide (NO) is a reactive endogenous molecule with multiple functions including inflammation and immunity. NO stimulates melanogenesis by activating soluble guanylyl cyclase (sGC) resulting in increases in intracellular guanosine 3′,5′‐cyclic monophosphate (cGMP). In vitro experiments showed that NO could inhibit the de novo attachment of melanocytes to extracellular matrix (ECM) suggesting that NO‐induced aberrant perturbation of melanocyte–ECM interaction could be a reason for melanocyte loss in vitiliginous lesions. Here, we examined whether there might be differences between normal melanocytes and vitiliginous melanocytes (VMs) with respect to NO‐induced detachment from ECM and whether cGMP is involved. We used the direct NO donor (Z)‐1‐[N‐(3‐ammoniopropyl)‐N‐(n‐propyl)amino]diazen‐1‐ium‐1,2‐diolate and the peroxynitrite donor 3‐morpholino‐sydnonimine for the present studies. These donors induced detachment of both normal melanocytes and non‐lesional VMs in a time‐ and concentration‐dependent manner with comparable susceptibility and similar expression profile of sGC. Treatment of melanocytes with caspase inhibitors reduced cell detachment, indicating that a major part of the detachment is due to apoptosis. The NO‐induced detachment but not apoptosis was partly inhibited in the presence of sGC and cGMP‐dependent protein kinase inhibitors. In addition, the membrane‐permeable cGMP analog 8‐(4‐chlorophenyethio/guanosine‐3′,5′‐cyclic monophosphate (PCPT) cGMP was not able to induce apoptosis in melanocytes, suggesting that NO‐induced detachment of melanocytes via apoptosis is cGMP‐independent. The present results also indicate that there are no apparent differences between NO‐induced detachment of non‐lesional vitiliginous and normal melanocytes from ECM.