Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells

Abstract

Human epidermal melanocytes as melanin producing skin cells represent a crucial barrier against UV-radiation and oxidative stress. It was shown that the intracellular signaling molecule cyclic guanosine-3 ,5 -monophosphate (cGMP), generated by the guanylyl cyclases (GCs), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) and the natriuretic peptide-activated particulate GC (GC-A/GC-B), plays a role in the melanocyte response to environmental stress. Importantly, cGMP is involved in NO-induced perturbation of melanocyte-extracellular matrix interactions and in addition, increased NO production during inflammation may lead to loss of melanocytes and support melanoma metastasis. Further, the NO-sensitive sGC is expressed predominantly in human melanocytes and non-metastatic melanoma cells, whereas absence of functional sGC but up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are detected in metastatic cells. Thus, suppression of sGC expression as well as up-regulated expression of GC-A/GC-B/iNOS appears to correlate with tumor aggressiveness. As the cGMP pathway plays important roles in melanocyte (patho)physiology, we present an overview on the differential effects of altered gravity (hypergravity/simulated microgravity) on the cGMP signaling pathway in melanocytes and melanoma cells with different metastatic potential. We believe that future experiments in real microgravity may benefit from considering cGMP signaling as a possible factor for melanocyte transformation and in medication.

Adaptive divergence in bill morphology and other thermoregulatory traits is facilitated by restricted gene flow in song sparrows on the California Channel Islands

“…The relationship between absorption of solar radiation and colour may explain the inclusion of putatively adaptive loci linked to genes involved in feather colour such as BCO2 , which is implicated in carotenoid‐processing in other passerines (Gazda et al, 2020; Toews et al, 2016), and the well‐studied coloration gene, Mc1r (Wolf Horrell et al, 2016). Other genes including MYRIP , RAB17 , and TRPC1 , further modify melanin synthesis, transportation, and deposition (Beaumont et al, 2011; Ivanova & Hemmersbach, 2020; Li et al, 2017; Wasmeier et al, 2008). Such results suggest that future studies should examine whether these genetic differences explain variation in plumage and feather traits across the archipelago.…”

The pigmentation phenotype of melanocytes affects their response to nitric oxide in vitro

“…Studies on in vitro cell models strongly suggest that NO present in the sur-Łukasz Marek, Irena Tam, Sławomir Kurkiewicz, Anna Dzierżęga-Lęcznar rounding cellular environment can affect melanocyte physiology in a paracrine and/or autocrine manner [12]. Importantly, no such effects were observed at low NO concentrations or for short-term exposure, whereas high NO concentrations were cytotoxic and decreased cell viability [13]. It has been reported that NO induces detachment of melanocytes from the extracellular matrix, which presumably contributes to pigment cell loss in vitiligo or melanoma metastasis [14][15][16].…”

Artificially altered gravity elicits cell homeostasis imbalance in planarian worms, and cerium oxide nanoparticles counteract this effect

“… 8 , 9 , 10 Hypergravity influences longevity in Drosophila , 11 and increases proliferation and differentiation of bone marrow stromal progenitors. 12 Moreover, several studies demonstrate that altered gravity affects signaling pathways 13 , 14 , 15 , 16 and modifies the transcriptional profile of factors not exclusively associated with stress response. 10 , 17 , 18 , 19 , 20 , 21 , 22 The understanding of the biological effects produced by altered gravity conditions is a relevant issue for spaceflight, bearing in mind that – after long‐term missions – astronauts experience a number of health problems, like atrophy of muscles, bone demineralization, cardiopulmonary, ocular and vestibular complications, and modifications in the nervous system connections.…”