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alpha-Tocopherol decreases the somatostatin receptor-effector system and increases the cyclic AMP/cyclic AMP response

A M Hernández-Pinto1, L Puebla-Jiménez, E Arilla-Ferreiro

  • 1Grupo de Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Crta. Madrid-Barcelona Km. 33.6, Universidad de Alcalá de Henares, E-28871 Alcalá de Henares, Madrid, Spain.

Neuroscience
|April 28, 2009
PubMed

Insights

Alpha-tocopherol enhances neuronal survival by reducing somatostatin receptor density, increasing cAMP levels, and activating CREB in the rat dentate gyrus. This vitamin modulates the somatostatinergic system to promote neuroprotection.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Neuronal survival is enhanced by alpha-tocopherol and modulated by cyclic AMP (cAMP).
  • Somatostatin (SST) receptors negatively regulate adenylyl cyclase (AC), decreasing cAMP levels.
  • The role of alpha-tocopherol in regulating the somatostatinergic system for neuronal survival is unclear.

Purpose of the Study:

  • To investigate the effects of alpha-tocopherol on the SST signaling pathway in the rat dentate gyrus.
  • To determine if alpha-tocopherol influences SST receptor expression and function.
  • To explore the impact of alpha-tocopherol on cAMP production and CREB activation.

Main Methods:

  • Rats were treated with alpha-tocopherol or vehicle.
  • SST-like immunoreactivity, mRNA, and receptor binding were assessed.
  • Protein levels of SST receptor subtypes, AC, G-proteins, and CREB were analyzed.
  • AC activity and SST's inhibitory effect on AC were measured.

Main Results:

  • Alpha-tocopherol decreased SST receptor density and protein levels of SSTR1-SSTR4 without altering mRNA.
  • The vitamin increased basal and forskolin-stimulated AC activity and reduced SST's inhibitory effect on AC.
  • Alpha-tocopherol decreased G-protein levels and enhanced ACVIII expression.
  • Levels of phosphorylated CREB (p-CREB) and total CREB increased following alpha-tocopherol treatment.

Conclusions:

  • Alpha-tocopherol modulates the somatostatinergic system by reducing SST receptor signaling.
  • Increased cAMP levels and CREB activation likely mediate the neuroprotective effects of alpha-tocopherol.
  • This study elucidates a novel mechanism for alpha-tocopherol-induced neuronal survival via the somatostatinergic pathway.

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