Stimulation of cloudman melanoma tyrosinase activity occurs predominantly in G2 phase of the cell cycle

Abdel‐Malek, Zalfa; Swope, Viki B.; Trinkle, Linda S.; Nordlund, James J.

doi:10.1016/0014-4827(89)90224-3

Cited by 23 publications

(13 citation statements)

References 16 publications

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“…Thus, cAMP production by ICB in eyes exposed to MSH might be one of the underlying mechanisms for the ocular hypotensive effect of MSH. This is in agreement with the fact that melanocortins act by activation of G protein coupled receptors and production of cAMP 16. Our study also found an increase in eicosanoid production by incubated ICB over a long incubation period.…”

Section: Discussionsupporting

confidence: 92%

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Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

Naveh

Kaplan-Messas²,

Marshall³

2000

British Journal of Ophthalmology

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Aim-To investigate whether the ocular hypotensive eVect of alpha melanocyte stimulating hormone (MSH) is related to eicosanoids or cyclic AMP (cAMP).Methods-Intraocular pressure (IOP) readings were taken at a similar time on the day before and after a single dose of topical MSH. Changes in the levels of prostaglandin E 2 (PGE 2 ) and prostacyclin in incubated iris ciliary body (ICB) explants were measured by specific radioimmunoassay (RIA). Incubated ICB explants were exposed to MSH or adrenaline (epinephrine) for a week. In addition, cAMP levels in the medium were determined following short term incubation using RIA. Results-A significant dose related reduction in IOP was noted with topical MSH (mean (SD) maximal eVect 4.5 (0.1) mm Hg (21%); p<0.001 v appropriate baseline) which persisted up to 6 hours (p=0.05). MSH treated ICB explants showed a 1.5-fold increase in PGE 2 and prostacyclin levels (p<0.001 for each parameter) while cAMP levels were increased twofold (p<0.001). Conclusions-A single application of MSH caused a sustained dose related ocular hypotensive eVect with no side eVects. An increase in eicosanoid and cAMP levels following ICB exposure to MSH indicated their involvement in MSH induced ocular hypotension. MSH and its analogues might have clinical relevance as antiglaucoma drugs with fewer side eVects because of their antiallergic and antiinflammatory properties. (Br J Ophthalmol 2000;84:1411-1414 Alpha melanocyte stimulating hormone (MSH) is a basic tridecapeptide which originates from pro-opiomelanocortin (POMC) found in the pituitary, 1 brain, 2 skin, 3 and at other sites. 4 POMC is the precursor for a family of biologically active peptides called melanocortins which include alpha, beta and gamma MSH, lipotropins, endorphins, and adrenocorticotrophic hormone (ACTH). MSH, named after its eVect on the pigmentation of amphibian skin, is involved in modulation of neuroprotection, anti-inflammatory activity, 5-7 and obesity regulation. 8 Its eVect is receptor specific and is not duplicated by ACTH, ACTH fragments, or glucocorticosteroids. 10In the eye MSH has been identified as a constitutive component of the normal aqueous humour of humans, rabbits, and mice.11 12 Its involvement in the regulation of intraocular pressure (IOP) was first noted in the 1960s and 1970s when high doses of the hormone were found to have a biphasic eVect on IOP. 13-15Melanocortins act by the activation of G protein coupled receptors and production of cyclic AMP (cAMP). 16 Cyclic AMP modulates IOP reduction by adrenergic agonists 17 18 and prostaglandin derivatives such as latanoprost.19 20 Enhancement of eicosanoid production by MSH treated ocular pigmented epithelium 21 is another possible role for melanocortins in the regulation on IOP. The activity of melanocortins in most organs is dose related so we have examined its role in IOP regulation using physiological doses, 22 23 unlike previous studies. 13-15 24-26 In this study we have investigated whether MSH causes a sustained reduction in IOP following a ...

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Section: Discussionsupporting

confidence: 92%

“…Melanocortins act by the activation of G protein coupled receptors and production of cyclic AMP (cAMP) 16. Cyclic AMP modulates IOP reduction by adrenergic agonists17 18 and prostaglandin derivatives such as latanoprost 19…”

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confidence: 99%

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

Naveh

Kaplan-Messas²,

Marshall³

2000

British Journal of Ophthalmology

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“…The effects of drugs on the cell cycle were examined in order to exclude the possibility that enhancement of tyrosinase resulted from arrest in the G2 phase (Abdel-Malek et al, 1989). Compared to control cells, the proportion of cells in G1 phase was higher in butyrate-, DMSO-, and DMF-treated samples (75.3%, 87.2%, 84.9%, and 85.3%, respectively), indicating a cytostatic arrest occurring at least partly in G1 ('Pable 5).…”

Section: Resultsmentioning

confidence: 99%

In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

Takahashi¹,

Parsons²

1990

Pigment Cell Research

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Sodium butyrate (butyrate), 5-azacytidine (5Aza-C), dimethyl sulfoxide (DMSO), and dimethyl formamide (DMF) were applied to a human melanoma cell line for the purpose of inducing pigmentation and terminal differentiation. The results are summarized as follows: 1) butyrate, DMSO, and DMF had a strong cytostatic effect, arresting cells in the G1 phase of the cycle; 2) butyrate caused a morphological change to spindle shape whereas DMSO and DMF produced rounded cells, without affecting the levels of vimentin and intermediate filaments; 3) tyrosinase activity and melanization were stimulated by DMSO and DMF but not by butyrate; 4) butyrate induced several membrane-bound enzyme activities (alkaline phosphatase and gamma-glutamyl transpeptidase); 5) changes in the expression of antigens related to tyrosinase activity (2B7 and 5C12) only partly corresponded to the changes in enzyme activity; 6) expression of the melanosomal B8G3 antigen was decreased by butyrate, DMSO, and DMF; and 7) the action of DMF resembled that of DMSO whereas 5Aza-C had little effect. The results indicate that these differentiating agents activate different sets of genes, the melanogenic pathway being activated independently of gamma-glutamyltranspeptidase. The down regulation of B8G3 antigen by these agents may provide a common focus for understanding the essential action of differentiation inducers in melanoma cells.

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“…On the other hand, the antimitogenic activity of psoralens in murine melanoma (Mengeaud and Ortonne, 1994) and other mammalian cells (Cohen et al, 1981) has been related with the arrest of the cell cycle (probably in the G2 phase) as a consequence of a cytostatic effect of the drug in W light-exposed cells. Abdel-Malek et al, (1989) demonstrated that the stimulation of melanogenesis by WMSH predominantly occurs in the G2 phase of murine melanoma cells. Accordingly, an increase in t.yrosinase activity was ob-is given between parentheses.…”

Section: Uvamentioning

confidence: 98%

Psoralen Activity and Binding Sites in Melanotic and Amelanotic Human Melanoma Cells

Isoldi

Scarparo

Schumacher

et al. 1999

Pigment Cell Research

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The biological activity and specific binding sites of 8-methoxypsoralen (8-MOP) are assayed using two human melanoma cell lines, melanotic SK-Mel 28 and amelanotic C32TG. Long-term (72 hr) treatment with 8-MOP at a concentration of 10(-4)M results in an increase in melanogenesis and a decrease in proliferation, similar in both cell lines. Daily exposure of these cells to ultraviolet A (UVA) irradiation (1.28 mJ/cm(2)) does not enhance the response to the compound. Daily pulse application (30 min daily) of 8-MOP does not promote any response. However, in combination with UVA, 8-MOP pulse treatment becomes as effective as the long-term treatment. A decrease in cell proliferation in the constant presence of 8-MOP is not coupled with apoptosis, since no increase in the number of apoptotic nuclei was observed after the treatment. The flow cytometry indicates that 8-MOP arrests the cells at the G0/G1 phase, irrespective of the presence or absence of UVA light. In view of the lack of epidermal growth factor (EGF) receptors in both cell lines, it is not likely that such an arrest is associated with the down-regulation of EGF receptors by 8-MOP. It is noted that this compound elicits a biphasic cell response, since cell proliferation increases after the first 24-hr treatment, whereas it decreases in the subsequent 48 hr and thereafter. Competition binding assays using 3H-8-MOP disclosed: 1) the specific binding of the compound in both cell lines occurs in the presence or absence of UVA light, and 2) a higher binding rate at low concentrations of the compound is in SK-Mel 28 (72%) rather than C32TG (58%) cells. The competition assays in the presence of UVA suggest a possible occurrence of covalent bindings between psoralen and receptor, as DNA covalent binding accounted to only 3-5% of the total binding in both cell lines.

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Stimulation of cloudman melanoma tyrosinase activity occurs predominantly in G2 phase of the cell cycle

Cited by 23 publications

References 16 publications

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

Psoralen Activity and Binding Sites in Melanotic and Amelanotic Human Melanoma Cells

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