Role of cyclic GMP signaling in the melanocyte response to hypergravity

The human skin acts as a first barrier of defense to protect the internal organs from various chemical and physical environmental stress factors like solar ultraviolet radiation (UV) and mechanical stimuli. Human melanocytes (located strategically in the basal layer of the skin epidermis) represent a crucial protective barrier against UV irradiation and oxidative stress by generating the radical-scavenging pigment melanin. However, melanin is also known to act as a photosensitizer that generates active oxygen species upon UV irradiation, which may initiate pigmentary disorders like vitiligo due to loss of melanocytes as well as oncogenic melanocyte transformation. Melanocytes may further act as a protective immune barrier at the dermo-epidermal junction and thus participate in immune surveillance. For melanocytes it is known that the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP) plays a key role in UVB-induced melanogenesis involving nitric oxide (NO) signaling. Moreover, cGMP is involved in NO-induced perturbation of melanocyte-extracellular matrix interactions that may lead to loss of melanocytes and support melanoma metastasis. In the frame of the current space exploration, investigations on the influence of altered gravity on melanocyte physiology are of special interest. As cGMP appears to play an important signaling role in melanocyte physiology, a brief overview is presented on the role of the guanylyl cyclase-cGMP signaling, with a focus on the melanocyte response to hypergravity. An estimation of the gravity impact on melanocyte function may be of importance to asses the risk of astronauts to develop pigmentary disorders, particularly melanoma and other relevant skin cancers, during long-term spaceflights.