Vitamin E deficiency impairs the somatostatinergic receptor-effector system and leads to phosphotyrosine phosphatase overactivation and cell death in the rat hippocampus.
Vitamin E plays an essential role in maintaining the structure and function of the nervous system, and its deficiency, commonly associated with fat malabsorption diseases, may reduce neuronal survival. We previously demonstrated that the somatostatinergic system, implicated in neuronal survival control, can be modulated by α-tocopherol in the rat dentate gyrus, increasing cyclic adenosine monophosphate response element binding protein phosphorylation. To gain a better understanding of the molecular actions of tocopherols and examine the link among vitamin E, somatostatin and neuronal survival, we have investigated the effects of a deficiency and subsequent administration of tocopherol on the somatostatin signaling pathway and neuronal survival in the rat hippocampus. No changes in somatostatin expression were detected in vitamin-E-deficient rats. These rats, however, showed a significant increase in the somatostatin receptor density and dissociation constant, which correlated with a significant increase in the protein levels of somatostatin receptors. Nevertheless, vitamin E deficiency impaired the ability of the somatostatin receptors to couple to the effectors adenylyl cyclase and phosphotyrosine phosphatase by diminishing Gi protein functionality. Furthermore, vitamin E deficiency significantly increased phosphotyrosine phosphatase activity and PTPη expression, as well as PKCδ activation, and decreased extracellular-signal-regulated kinase phosphorylation. All these changes were accompanied by an increase in neuronal cell death. Subsequent α-tocopherol administration partially or completely reversed all these values to control levels. Altogether, our results prove the importance of vitamin E homeostasis in the somatostatin receptor-effector system and suggest a possible mechanism by which this vitamin may regulate the neuronal cell survival in the adult hippocampus.
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vitamin E somatostatin α-tocopherol cyclic adenosine monophosphate tocopherols vitamin E somatostatin tocopherol somatostatin somatostatin Vitamin E vitamin-E somatostatin Vitamin E phosphotyrosine somatostatin receptors somatostatin receptors phosphotyrosine phosphatase Gi protein phosphotyrosine phosphatase PTPη somatostatin PKCδ extracellular-signal-regulated kinase somatostatin receptor cyclic adenosine monophosphate response element binding protein somatostatin somatostatin somatostatin somatostatin receptor somatostatinergic receptor phosphotyrosine phosphatase vitamin E somatostatin adenylyl phosphotyrosine vitamin E phosphotyrosine α-tocopherol