Einfluss von Hypergravitation auf den cGMP-Efflux in Stickstoffmonoxid-stimulierten humanen Melanozyten und Melanomzellen
type: CreativeWork
description: Gravity alteration is known to affect cell proliferation, morphology, gene expression, and me-tabolism. To our knowledge, studies concerning the gravity influence on melanocyte physiol-ogy with respect to activation and cellular responses that are important for malignant trans-formation have been rarely reported. Since melanocytes are able to sense mechanical forces and transform them into biochemical signals it was assumed that these cells likewise respond to gravity alteration. We examined whether hypergravity (up to 5g for 24 h) modulates the efflux of the second messenger cGMP under conditions of stimulated cGMP-synthesis. Due to the differential expression of functional guanylyl cyclase (GC) isoforms in normal human melanocytes (NHM) and melanoma cell lines we used direct NO donors (NONOates) which differ in their kinetics of NO release as stimulators of sGC and ANP as a GC-A modulator. Our results demonstrate that long-term application of hypergravity (5g for 24 h) in the presence of DETA/NO induced a decrease in intracellular cGMP in NHMs and non-metastatic 1F6 melanoma cells compared to cGMP levels at 1g. The corresponding extracellular cGMP levels increased suggesting that hypergravity enhances the cGMP efflux. This efflux was re-duced in the presence of trequinsin as a selective phosphodiesterase 5 inhibitor and additionally a highly selective inhibitor of multidrug resistance protein 4/5, indicating that in melanocytes the hypergravity-stimulated cGMP efflux under PDE5 inhibition is most proba-bly mediated by endogenous anion transporters and/or selective cGMP transporters like MRP 4/5. Short-term application (5g up to 6 h) was not effective. Compared to the 1g-controls there existed no differences between intra- and extracellular cGMP-levels. These results indicate that short-term centrifugation did not affect cGMP efflux in melanocytic cells. Interestingly, highly metastatic melanoma cells were apparently insensitive to a 24 hour centrifugation in the p…
abstract: Gravity alteration is known to affect cell proliferation, morphology, gene expression, and me-tabolism. To our knowledge, studies concerning the gravity influence on melanocyte physiol-ogy with respect to activation and cellular responses that are important for malignant trans-formation have been rarely reported. Since melanocytes are able to sense mechanical forces and transform them into biochemical signals it was assumed that these cells likewise respond to gravity alteration. We examined whether hypergravity (up to 5g for 24 h) modulates the efflux of the second messenger cGMP under conditions of stimulated cGMP-synthesis. Due to the differential expression of functional guanylyl cyclase (GC) isoforms in normal human melanocytes (NHM) and melanoma cell lines we used direct NO donors (NONOates) which differ in their kinetics of NO release as stimulators of sGC and ANP as a GC-A modulator. Our results demonstrate that long-term application of hypergravity (5g for 24 h) in the presence of DETA/NO induced a decrease in intracellular cGMP in NHMs and non-metastatic 1F6 melanoma cells compared to cGMP levels at 1g. The corresponding extracellular cGMP levels increased suggesting that hypergravity enhances the cGMP efflux. This efflux was re-duced in the presence of trequinsin as a selective phosphodiesterase 5 inhibitor and additionally a highly selective inhibitor of multidrug resistance protein 4/5, indicating that in melanocytes the hypergravity-stimulated cGMP efflux under PDE5 inhibition is most proba-bly mediated by endogenous anion transporters and/or selective cGMP transporters like MRP 4/5. Short-term application (5g up to 6 h) was not effective. Compared to the 1g-controls there existed no differences between intra- and extracellular cGMP-levels. These results indicate that short-term centrifugation did not affect cGMP efflux in melanocytic cells. Interestingly, highly metastatic melanoma cells were apparently insensitive to a 24 hour centrifugation in the p…
author: Stieber, Christiane Claudia
language: ger
keywords: info:eu-repo/classification/ddc/570, Biowissenschaften, Biologie, Hypergravitation, Stickstoffmonoxid, Melanozyten, cGMP
date published: 2007
date modified: 2026-07-30T19:43:10Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University