VIP and peptides related to activity-dependent neurotrophic factor protect PC12 cells against oxidative stress.
Oxidative stress is a common associative mechanism that is part of the pathogenesis of many neurodegenerative diseases. Vasoactive intestinal peptide (VIP) is a principal neuropeptide associated with normal development and aging. We have previously reported that VIP induced the secretion of proteins from glial cells, including the novel survival-promoter: activity-dependent neurotrophic factor (ADNF). ADNF-9, a nine amino acid peptide derived from ADNF, protects neurons from death caused by various toxins. In the present study, we examined the neuroprotective effect of VIP against oxidative stress in a pheochromocytoma cell line (PC12). In addition, a lipophilic derivative of VIP, Stearyl-Nle17-VIP (SNV), and two femtomolar-acting peptides: ADNF-9 and a 70% homologous peptide to ADNF-9, NAP were tested as well. PC12 cells were treated with 100 microM H2O2 for 24 h resulting in a reduction in cell survival to 35-50% as compared to controls. Addition of VIP or SNV prior and during the exposure to100 microM H2O2 increased cell survival to 80-90% of control values. Culture treatment with ADNF-9 or NAP in the presence of 100 microM H2O2 increased cell survival to 75-80% of control values. Messenger RNA expression analysis revealed that incubation with VIP resulted in a twofold increase in VIP mRNA, whereas NAP treatment did not cause any change in VIP expression, implicating different mechanisms of action. Furthermore, addition of an ADNF-9 antibody prevented the ability of VIP to protect against oxidative stress, suggesting that VIP protection is partially mediated via an ADNF-like protein.
Steingart
R A
RA
Department of Clinical Biochemistry, Sackler Medical School, Tel Aviv University, Israel.
Solomon
B
B
Brenneman
D E
DE
Fridkin
M
M
Gozes
I
I
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000235:genetics / Q000494:pharmacology*
D000906:Antibodies; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; C086770:stearyl-norleucine(17)-vasoactive intestinal peptide; D014660:Vasoactive Intestinal Peptide; D006861:Hydrogen Peroxide; C425904:davunetide