Melatonin triggers PKA activation in the rodent malaria parasite Plasmodium chabaudi.

作者: Marcos L. Gazarini , Flávio H. Beraldo , Fabiana M. Almeida , Martin Bootman , Aline M. Da Silva

DOI: 10.1111/J.1600-079X.2010.00810.X

关键词: Cell biologyCalciumMelatoninEnzyme activatorPlasmodium chabaudiBAPTAParasitemiaProtein kinase AInternal medicineBiologyStimulationEndocrinology

摘要: Calcium (Ca(2+) ) is a critical regulator of many aspects the Plasmodium reproductive cycle. In particular, intra-erythrocyte parasites respond to circulating levels melatonin in process mediated partly by intracellular Ca(2+) . Melatonin promotes development and synchronicity parasites, thereby enhancing their spread worsening clinical implications. The signalling mechanisms underlying effects are not fully established, although both cyclic AMP (cAMP) have been implicated. Furthermore, it clear whether different strains use same, or divergent, signals control development. aim this study was explore engaged P. chabaudi, virulent rodent parasite. Using at throphozoite stage acutely isolated from mice erythrocytes, we demonstrate that triggers cAMP production protein kinase A (PKA) activation. Interestingly, stimulation cAMP/PKA dependent on elevation within parasite, because buffering changes using chelator BAPTA prevented response melatonin. Incubation with evoked robust as did application membrane-permeant analogue cAMP. Our data suggest P. chabaudi engages systems when stimulated there positive feedback between these messengers, evokes vice versa. more than doubled observed extent parasitemia, increase concentration PKA activation essential for effect. These support possibility antagonists derivates therapeutic approach.

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