In Vitro Stimulation of Protein Kinase C by Melatonin |
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Authors: | Antón-Tay Fernando Ramírez Gerardo Martínez Isabel Benítez-King Gloria |
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Institution: | (1) Departamento de Biología de la Reproducción, CBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico;(2) Departamento de Neurofarmacología, DIC, Instituto Mexicano de Psiquiatría, México, D.F, México |
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Abstract: | It has been shown that melatonin through binding to calmodulin acts both in vitro and in vivo as a potent calmodulin antagonist. It is known that calmodulin antagonists both bind to the hydrophobic domain of Ca2+ activated calmodulin, and inhibit protein kinase C activity. In this work we explored the effects of melatonin on Ca2+ dependent protein kinase C activity in vitro using both a pure commercial rat brain protein kinase C, and a partially purified enzyme from MDCK and N1E-115 cell homogenates. The results showed that melatonin directly activated protein kinase C with a half stimulatory concentration of 1 nM. In addition the hormone augmented by 30% the phorbol ester stimulated protein kinase C activity and increased 3H] PDBu binding to the kinase. In contrast, calmodulin antagonists (500 M) and protein kinase C inhibitors (100 M) abolished the enzyme activity. Melatonin analogs tested were ineffective in increasing either protein kinase C activity or 3H] PDBu binding. Moreover, the hormone stimulated protein kinase C autophosphorylation directly and in the presence of phorbol ester and phosphatidylserine. The results show that besides the melatonin binding to calmodulin, the hormone also interacts with protein kinase C only in the presence of Ca2+. They also suggest that the melatonin mechanism of action may involve interactions with other intracellular hydrophobic and Ca2+ dependent proteins. |
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Keywords: | Melatonin protein kinase C calcium MDCK N1E-115 autophosphorylation mechanism of action |
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