Activity-dependent neuroprotective protein (ADNP)-derived peptide (NAP) ameliorates hypobaric hypoxia induced oxidative stress in rat brain.

Abstract

Hypobaric hypoxia is a socio-economic problem affecting cognitive, memory and behavior functions. Severe oxidative stress caused by hypobaric hypoxia adversely affects brain areas like cortex, hippocampus, basal ganglia, and cerebellum. In the present study, we have investigated the antioxidant and memory protection efficacy of the synthetic NAP peptide (NAPVSIPQ) during long-term chronic hypobaric hypoxia (7, 14, 21 and 28 days, 25,000ft) in rats. Intranasal supplementation of NAP peptide (2μg/Kg body weight) improved antioxidant status of brain evaluated by biochemical assays for free radical estimation, lipid peroxidation, GSH and GSSG level. Analysis of expression levels of SOD revealed that NAP significantly activated antioxidant genes as compared to hypoxia exposed rats. We have also observed a significant increased expression of Nrf2, the master regulator of antioxidant defense system and its downstream targets such as HO-1, GST and SOD1 by NAP supplementation, suggesting activation of Nrf2-mediated antioxidant defense response. In corroboration, our results also demonstrate that NAP supplementation improved the memory function assessed with radial arm maze. These cumulative results suggest the therapeutic potential of NAP peptide for ameliorating hypobaric hypoxia-induced oxidative stress.

• Authors: Narendra K Sharma, Niroj K Sethy, Ram Niwas Meena, Govindsamy Ilavazhagan, Mainak Das, Kalpana Bhargava
• Journal: Peptides (Peptides) Vol. 32 Issue 6 Pg. 1217-24 (Jun 2011) ISSN: 1873-5169 [Electronic] United States
• PMID: 21453737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Free Radicals
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Oligopeptides
• RNA, Messenger
• Malondialdehyde
• Heme Oxygenase-1
• Sod1 protein, rat
• Superoxide Dismutase
• Superoxide Dismutase-1
• Glutathione
• davunetide
• Glutathione Disulfide

Topics

• Administration, Intranasal
• Altitude Sickness (drug therapy, metabolism, physiopathology)
• Animals
• Brain (drug effects, physiopathology)
• Free Radicals (metabolism)
• Glutathione (metabolism)
• Glutathione Disulfide (metabolism)
• Heme Oxygenase-1 (biosynthesis)
• Hypoxia (drug therapy, metabolism, physiopathology)
• Lipid Peroxidation (drug effects)
• Male
• Malondialdehyde (analysis)
• Maze Learning (drug effects, physiology)
• Memory (drug effects, physiology)
• NF-E2-Related Factor 2 (biosynthesis)
• Neuroprotective Agents (administration & dosage, chemical synthesis)
• Oligopeptides (administration & dosage, chemical synthesis)
• Oxidative Stress (drug effects)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Superoxide Dismutase (biosynthesis)
• Superoxide Dismutase-1