Differential Expression of Functional Guanylyl Cyclases in Melanocytes: Absence of Nitric-Oxide-Sensitive Isoform in Metastatic Cells

Ivanova, Krassimira; Das, Partha; Wijngaard, R.M.J.van den; Lenz, W.; Klockenbring, Torsten; Malcharzyk, V.; Drummer, C.; Gerzer, R.

doi:10.1046/j.1523-1747.2001.01255.x

Cited by 18 publications

(30 citation statements)

References 45 publications

(52 reference statements)

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“…p53 and p21 expression, cell cycle distribution, and the level of apoptosis after cisplatin treatment were not altered by either ODQ or 8-bromo-cGMP. Furthermore, melanoma cells frequently do not express the NO-sensitive isoform of soluble guanylyl cyclase, which responds to NO to generate cGMP and subsequently induce p21 expression (62). Taken together, these data strongly suggests that p21 is activated in a p53-dependent manner in melanoma cells with wild type p53 and that the cGMP signaling pathway is not involved.…”

Section: Inhibition Of P53 By the Expression Of Dominant Negative P53mentioning

confidence: 89%

Depletion of Endogenous Nitric Oxide Enhances Cisplatin-induced Apoptosis in a p53-dependent Manner in Melanoma Cell Lines

Tang¹,

Grimm

2004

Journal of Biological Chemistry

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The expression of inducible nitric-oxide synthase in melanoma tumor cells was recently shown to correlate strongly with poor patient survival after combination biochemotherapy (p < 0.001). Furthermore, evidence suggests that nitric oxide, a reaction product of nitricoxide synthase, exhibits antiapoptotic activity in melanoma cells. We therefore hypothesized that nitric oxide antagonizes chemotherapy-induced apoptosis. Whether nitric oxide is capable of regulating cell growth and apoptotic responses to cisplatin treatment in melanoma cell lines was evaluated. We demonstrate herein that depletion of endogenously produced nitric oxide can inhibit melanoma proliferation and promote apoptosis. Moreover, our data indicate that the depletion of nitric oxide leads to changes in cell cycle regulation and enhances cisplatin-induced apoptosis in melanoma cells. Strikingly, we observed that the depletion of nitric oxide inhibits cisplatin-induced wild type p53 accumulation and p21Waf1/Cip1/Sdi1 expression in melanoma cells. When cisplatin-induced p53 binding to the p21 Waf1/Cip1/Sdi1 promoter was examined, it was found that nitric oxide depletion significantly reduced the presence of p53-DNA complexes after cisplatin treatment. Furthermore, dominant negative inhibition of p53 activity enhanced cisplatin-induced apoptosis. Together, these data strongly suggest that endogenously produced nitric oxide is required for cisplatin-induced p53 activation and p21Waf1/Cip1/Sdi1 expression, which can regulate melanoma sensitivity to cisplatin.

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Section: Inhibition Of P53 By the Expression Of Dominant Negative P53mentioning

confidence: 89%

Depletion of Endogenous Nitric Oxide Enhances Cisplatin-induced Apoptosis in a p53-dependent Manner in Melanoma Cell Lines

Tang¹,

Grimm

2004

Journal of Biological Chemistry

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“…RNA extraction and reverse transcription polymerase chain reaction (RT-PCR) were performed as reported previously (Ivanova et al 2001). Briefly, total RNA was isolated from melanocyte culture by the RNAClean System (Angewandte Gentechnologie Systeme, Heidelberg, Germany) following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…We previously have reported differential expression of guanylyl cyclase isoforms in melanocytic cells. NHMs and vitiliginous melanocytes (VMs) and nonmetastatic melanoma cell lines predominantly express the NO-sensitive sGC that appears to be associated with melanogenesis (Ivanova et al 2001(Ivanova et al , 2005. In contrast, human metastatic melanoma cell lines lack the β 1 subunit of the NO-sensitive sGC which can lead to a loss of NO sensitivity in control mechanisms involving the NO-sGC-cGMP signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, human metastatic melanoma cell lines lack the β 1 subunit of the NO-sensitive sGC which can lead to a loss of NO sensitivity in control mechanisms involving the NO-sGC-cGMP signaling pathway. On the other hand, the activities of the natriuretic peptide-sensitive GC-A and GC-B isoforms are upregulated in metastatic melanoma cell lines (Ivanova et al 2001). Although the exact nature of this activation remains to be elucidated, the existence of such differential cGMP pools may contribute to the specific effects of NO on melanocyte function.…”

Section: Introductionmentioning

confidence: 99%

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Immortalization of human melanocytes does not alter the de novo properties of nitric oxide to induce cell detachment from extracellular matrix components via cGMP

Ivanova

Lambers

Wijngaard

et al. 2008

In Vitro Cell.Dev.Biol.-Animal

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Nitric oxide (NO) is an important mediator in many (patho)physiological processes including inflammation and skin cancer. A key transducer in NO signaling is the soluble guanylyl cyclase (sGC) that catalyzes the formation of guanosine 3',5'-cyclic monophosphate (cGMP). The basic mechanism of NO-cGMP signaling in melanocytic cells is, however, not well elucidated. A setback for such studies is the limited availability of patient-derived melanocytes. Here, we report that immortalized human normal and vitiliginous cell lines generated via cell transfection with human papilloma virus 16 genes E6 and E7 express NO synthase and guanylyl cyclase isoforms and the multidrug resistance-associated proteins 4 and 5 as selective cGMP exporters. Donors of NO (e.g., the NONOate (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NO) and reactive nitrogen oxygen species (RNOS) like 3-morpholino-sydnonimine (SIN-1) as a donor of peroxynitrite as well as YC-1 as a NO-independent sGC stimulator increased intracellular cGMP levels in immortalized melanocytes (up to eightfold over controls), indicating the expression of functional sGC in these cells. PAPA-NO and SIN-1 also reduced the attachment of immortalized melanocytes to extracellular matrix (ECM) components like fibronectin which was dependent on cellular melanin content and cGMP. Such effects on melanoma cells were positively related to metastatic potential and were cGMP independent. Intriguingly, nonpigmented metastatic melanoma cells were more sensitive to exogenous sources of RNOS than of NO. Thus, immortalized melanocytes can be used as a tool for further research on differences in cell signaling between the different melanocytic lineages in particular towards impairment of cell-ECM adhesion by NO or RNOS, which may be important in metastasis and vitiligo pathogenesis.

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“…The family comprises both membrane-bound and soluble isoforms that are expressed in nearly all cell types. Both forms differ in structure, mechanism of activation and subcellular localization (Ivanova et al 2001). The membrane-bound form (pGC) is a monomer that is stimulated by different peptide hormones.…”

mentioning

confidence: 99%

Guanylyl cyclase activity during photoperiodic flower induction in Pharbitis nil

et al. 2008

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It is known that the level of cGMP is modulated in plant cells in response to a number of stimuli but intracellular events dependent on cGMP metabolism are not clear. Guanylyl cyclases (GCs) are enzymes which are responsible for synthesis of cGMP in eukaryotic and prokaryotic cells. To collect evidence for the participation of cGMP in light signal transduction we isolated enzyme with guanylyl cyclase activity from Pharbitis nil and analysed its level and activity during photoperiodic flower induction. Soluble proteins were isolated from seedlings of a model short-day plant P. nil, partly purified and identified by in vivo and in vitro enzyme assay. In green plants enzyme activity amounted to 484 nmol cGMP/min/mg protein, whereas in etiolated plants it was three times lower (158 nmol cGMP/min/mg protein). Analyse cyclase consists of a single polypeptide of Mr 40 kDa. In order to determine if changes in guanylyl cyclase activity occurred in response to a long, inductive night, we measured enzyme activity in 4-h intervals and observed its increase at 4, 8 and 16 h of darkness. This pattern also fits well with changes in the endogenous cGMP level during a 16 h long flower inductive night. Immunocytochemical analysis confirmed these observations and revealed that changes in the GC level during light/ dark conditions appeared. During 16 h long inductive night the strongest signal was observed in cotyledons after 4 and 16 h of the darkness. A high level of fluorescence was generally distributed in mesophyll, however, it was also observed in guard cells. Staining was apparently absent in the veins and cotyledon body. Furthermore, the location inside the cell was analysed. The protein was immunolocalized preferentially in the cytosol, chloroplasts and peroxysomes. Taken together, these data demonstrate in Pharbitis nil the presence of an enzyme which is able to convert GTP to cGMP. Because its level and activity are affected by light we believe that GC/cGMP play a substantial role in light/dark dependent process in plants, such as photoperiodic flower induction.

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Differential Expression of Functional Guanylyl Cyclases in Melanocytes: Absence of Nitric-Oxide-Sensitive Isoform in Metastatic Cells

Cited by 18 publications

References 45 publications

Depletion of Endogenous Nitric Oxide Enhances Cisplatin-induced Apoptosis in a p53-dependent Manner in Melanoma Cell Lines

Depletion of Endogenous Nitric Oxide Enhances Cisplatin-induced Apoptosis in a p53-dependent Manner in Melanoma Cell Lines

Immortalization of human melanocytes does not alter the de novo properties of nitric oxide to induce cell detachment from extracellular matrix components via cGMP

Guanylyl cyclase activity during photoperiodic flower induction in Pharbitis nil

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