A femtomolar-acting neuroprotective peptide induces increased levels of heat shock protein 60 in rat cortical neurons: a potential neuroprotective mechanism

• Published in: Neuroscience letters 1999-04, Vol.264 (1), p.9-12
• Main Authors: Zamostiano, Rachel, Pinhasov, Albert, Bassan, Merav, Perl, Orly, Steingart, Ruth A., Atlas, Roy, Brenneman, Douglas E., Gozes, Illana
• Format: Article
• Language: English
• Subjects: Activity-dependent neurotrophic factor; Amyloid beta-Peptides - pharmacology; Animals; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chaperonin 60 - antagonists & inhibitors; Chaperonin 60 - metabolism; hsp60; Medical sciences; Nerve Tissue Proteins - pharmacology; Neurons; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; Osmolar Concentration; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Rats; Stress proteins
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00168-8

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 β-amyloid peptide, reduced the amount of intracellular hsp60. Treatment with ADNF-9 prevented the reduction in hsp60 produced by the β-amyloid peptide. The protection against the β-amyloid peptide-associated cell death provided by ADNF-9 may be mediated in part by intracellular increases in hsp60.