Institute of Aerospace Medicine, Department of Gravitational Biology, German Aerospace Center (DLR), Linder Hoehe, 51147 Cologne, Germany.
Int J Mol Sci. 2020 Feb 8;21(3):1139. doi: 10.3390/ijms21031139.
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.
人类表皮黑素细胞作为产生黑色素的皮肤细胞，是抵御紫外线辐射和氧化应激的关键屏障。有研究表明，细胞内信号分子环鸟苷酸-3'，5'-单磷酸（cGMP），由鸟苷酸环化酶（GCs）产生，例如，一氧化氮（NO）敏感可溶性 GC（sGC）和利钠肽激活的颗粒 GC（GC-A/GC-B），在黑素细胞对环境应激的反应中发挥作用。重要的是，cGMP 参与了 NO 诱导的黑素细胞-细胞外基质相互作用的改变，此外，炎症期间 NO 产量的增加可能导致黑素细胞丢失，并支持黑色素瘤转移。此外，NO 敏感的 sGC 主要在人黑素细胞和非转移性黑素瘤细胞中表达，而功能性 sGC 缺失但 GC-A/GC-B 和诱导型一氧化氮合酶（iNOS）表达上调则在转移性细胞中检测到。因此，sGC 表达的抑制以及 GC-A/GC-B/iNOS 的上调表达似乎与肿瘤侵袭性相关。由于 cGMP 途径在黑素细胞（病理）生理学中发挥重要作用，我们综述了改变重力（超重力/模拟微重力）对具有不同转移潜能的黑素细胞和黑素瘤细胞中 cGMP 信号通路的影响。我们相信，未来在真实微重力下的实验可能会受益于将 cGMP 信号作为黑素细胞转化和药物治疗的一个可能因素。
