VIP-Related protection against lodoacetate toxicity in pheochromocytoma (PC12) cells: a model for ischemic/hypoxic injury

J Mol Neurosci. 2000 Dec;15(3):147-54. doi: 10.1385/JMN:15:3:147.


To evaluate the protective properties of peptides related functionally and/or structurally to vasoactive intestinal peptide (VIP), PC12 cultures were treated with iodoacetate as a model for neuronal ischemic/hypoxic injury. Brain tissue can be pre-conditioned against lethal ischemia by several mechanisms including sub-lethal ischemia, moderate hypoglycemia, heat shock, and growth factors. In the present study, a superactive VIP lipophilic analog (Stearyl-Norleucine17-VIP; SNV) was used to pre-condition media of PC12 cells. After removal of the conditioned media, the cultures were exposed to iodoaceate, which inhibits glycolysis. Protective efficacy against iodoacetate-induced injury was assessed by the measurements of lactate dehydrogenase (LDH) activity in the media. Treatment with iodoacetate for 2.5 h produced a twofold increase in LDH activity in the media. The protective effect of SNV had an EC50 of 1 pM. Comparison of the preconditioning time required for full protection by SNV showed no apparent difference between a 15 min and a 2 h incubation period prior to the addition of iodoacetate. Iodoacetate treatment produced a 20% decrease in the RNA transcripts encoding activity-dependent neuroprotective protein (ADNP), a novel glia-derived protein that is regulated by VIP. The iodoacetate-associated reduction in ADNP mRNA was prevented by pre-treatment with SNV. These effects imply that SNV provides a regulatory mechanism for ADNP synthesis during glycolytic stress. Furthermore, a short exposure to SNV provided potent protection from iodoacetate-induced toxicity suggesting that SNV may have therapeutic value in the treatment of ischemic/hypoxic injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Disease Models, Animal
  • Enzyme Inhibitors / toxicity*
  • Homeodomain Proteins*
  • Iodoacetates / toxicity*
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Nerve Tissue Proteins / genetics
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / antagonists & inhibitors
  • PC12 Cells / cytology
  • PC12 Cells / drug effects*
  • PC12 Cells / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Vasoactive Intestinal Peptide / pharmacology*


  • Enzyme Inhibitors
  • Homeodomain Proteins
  • Iodoacetates
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Neurotoxins
  • RNA, Messenger
  • stearyl-norleucine(17)-vasoactive intestinal peptide
  • Vasoactive Intestinal Peptide