A femtomolar-acting neuroprotective peptide induces increased levels of heat shock protein 60 in rat cortical neurons: a potential neuroprotective mechanism.
Activity-dependent neurotrophic factor (ADNF) was recently isolated from conditioned media of astrocytes stimulated with vasoactive intestinal peptide (VIP). ADNF provided neuroprotection at femtomolar concentration against a wide variety of toxic insults. A nine amino acid peptide (ADNF-9) captured with even greater potency the neuroprotective activity exhibited by the parent protein. Utilizing Northern and Western blot analyses, it was now shown that ADNF-9 increased the expression of heat shock protein 60 (hsp60) in rat cerebral cortical cultures. In contrast, treatment with the Alzheimer's toxin, the beta-amyloid peptide, reduced the amount of intracellular hsp60. Treatment with ADNF-9 prevented the reduction in hsp60 produced by the beta-amyloid peptide. The protection against the beta-amyloid peptide-associated cell death provided by ADNF-9 may be mediated in part by intracellular increases in hsp60.
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats