Anti-apoptotic actions of vasopressin in H32 neurons involve MAP kinase transactivation and Bad phosphorylation

Exp Neurol. 2008 Jun;211(2):529-38. doi: 10.1016/j.expneurol.2008.02.023. Epub 2008 Mar 10.

Abstract

Vasopressin (VP) secreted within the brain modulates neuronal function acting as a neurotransmitter. Based on the observation that VP prevented serum deprivation-induced cell death in the neuronal cell line, H32, which expresses endogenous V1 receptors, we tested the hypothesis that VP has anti-apoptotic properties. Flow cytometry experiments showed that 10 nM VP prevented serum deprivation-induced cell death and annexin V binding. Serum deprivation increased caspase-3 activity in a time and serum concentration dependent manner, and VP prevented these effects through interaction with receptors of V1 subtype. The signaling pathways mediating the anti-apoptotic effect of VP involve mitogen activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK), Ca(2+)/calmodulin dependent kinase (CaMK) and protein kinase C (PKC). Western blot analyses revealed time-dependent decreases of Bad phosphorylation and increases in cytosolic levels of cytochrome c following serum deprivation, effects which were prevented by 10 nM VP. These data demonstrate that activation of endogenous V1 VP receptors prevents serum deprivation-induced apoptosis, through phosphorylation-inactivation of the pro-apoptotic protein, Bad, and consequent decreases in cytosolic cytochrome c and caspase-3 activation. The data suggest that VP has anti-apoptotic activity in neurons and that VP may act as a neuroprotective agent in the brain.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / pharmacology
  • Apoptosis Regulatory Proteins / physiology*
  • Cell Line
  • Chick Embryo
  • Enzyme Activation / physiology
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / enzymology
  • Neurons / metabolism*
  • Phosphorylation
  • Transcriptional Activation / physiology*
  • Vasopressins / pharmacology
  • Vasopressins / physiology*
  • bcl-Associated Death Protein / antagonists & inhibitors
  • bcl-Associated Death Protein / metabolism*
  • bcl-Associated Death Protein / physiology

Substances

  • Apoptosis Regulatory Proteins
  • bcl-Associated Death Protein
  • Vasopressins
  • Mitogen-Activated Protein Kinases