Role of Bcl-2 in the regulation of CREB activity and vasopressin expression in hypothalamic neurons |
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Authors: | L. S. Nikitina E. V. Chernigovskaya N. A. Dorofeeva O. D. Kirillova M. V. Glazova |
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Affiliation: | 1.Sechenov Institute of Evolutionary Physiology and Biochemistry,Russian Academy of Sciences,St. Petersburg,Russia |
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Abstract: | For the last years, data have appears that indicate that functions of the antiapoptotic protein Bcl-2 are not restricted by its role in prevention of apoptosis. Earlier we showed that Bcl-2 participated in regulation of synthesis and secretion of vasopressin by neurons of magnocellular hypothalamic nuclei. Based on our previous works about effect of administration of the Bcl-2 blocker HA-14-1 on activities of the ERK1/2 cascade and of the transcriptional factor CREB in hypothalamic vasopressinergic neurons, we formulated hypothesis about the mediated action of Bcl-2 on vasopressin biosynthesis by transcription factor CREB and/or the ERK1/2 signal cascade. In the presented work we studied effects of Bcl-2 inactivation on vasopressin expression and activity of the ERK1/2 cascade and CREB in experiments on briefly incubated hypothalamus slides containing supraoptic nuclei. We have shown that inactivation of Bcl-2 in vitro by the blocker HA14-1 led to a decrease in the CREB activity, reduced significantly the vasopressin mRNA level, and increased the vasopressin content in the supraoptic nucleus neurons, with the ERK1/2 cascade activity being increased. Effect of Bcl-2 on the vasopressin synthesis activity did not depend on activity of the ERK1/2 signal cascade. Thus, Bcl-2 has been shown to play an activating role in control of vasopressin neurons of the hypothalamus supraoptic nucleus. The presented data confirm that effect of Bcl-2 on vasopressin synthesis by the supraoptic nucleus neurons is mediated by its ability to control activity of the transcriptional factor CREB. |
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