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- Title
Differential Expression of Functional Guanylyl Cyclases in Melanocytes: Absence of Nitric-Oxide-Sensitive Isoform in Metastatic Cells.
- Authors
Ivanova, Krassimira; Das, Pranab K.; van den Wijngaard, Rene M. J. G. J.; Lenz, Wolfgang; Klockenbring, Torsten; Malcharzyk, Vanessa; Drummer, Christian; Gerzer, Rupert
- Abstract
Summary Nitric oxide (NO) is a reactive endogenous molecule with multiple functions and its cellular signaling activity is mainly mediated by activation of the soluble isoform of guanylyl cyclase, a heterodimeric (α/β) hemeprotein. The expression of the NO-sensitive soluble isoform of guanylyl cyclase was studied in various cultured melanocytic cells by measuring the accumulation of guanosine 3′,5′-cyclic monophosphate in the presence and absence of NO donors. Here we report that 3-morpholino-sydnonimine, a donor of NO redox species, and (Z)-1-[2- (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, a direct NO donor, induced a 20-fold increase in intracellular guanosine 3′,5′-cyclic monophosphate in nonmetastatic melanoma cells and normal melanocytes in culture that could be related to cellular melanin content in a concentration-dependent manner. The increased intracellular guanosine 3′,5′-cyclic monophosphate was due to stimulation of the activity of soluble guanylyl cyclase as such increase was completely abolished by using a specific inhibitor of soluble guanylyl cyclase. The involvement of functional soluble guanylyl cyclase was further confirmed by the presence of α1 and β1 subunits in these cells at both mRNA and protein levels. In contrast, none of the NO donors induced guanosine 3′,5′-cyclic monophosphate production in metastatic melanoma cells, which could be attributed to the absence of the β1 subunit that is essential for catalytic activity of the soluble isoform of guanylyl cyclase. Metastatic melanoma cells produced higher levels of intracellular guanosine 3′,5′-cyclic monophosphate in response to natriuretic peptides than other cell types, however, due to upregulation of membrane-bound guanylyl cyclase activities, but they are less pigmented or unpigmented. The present finding suggests that NO...
- Subjects
MELANOCYTES; CYCLIC guanylic acid
- Publication
Journal of Investigative Dermatology, 2001, Vol 116, Issue 3, p409
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1046/j.1523-1747.2001.01255.x