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Journal of Molecular Neuroscience

, Volume 42, Issue 3, pp 397–403 | Cite as

Regulation of Oxidative Stress by Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Mediated by PACAP Receptor

  • Hirokazu Ohtaki
  • Atsushi Satoh
  • Tomoya Nakamachi
  • Sachiko Yofu
  • Kenji Dohi
  • Hiroyoshi Mori
  • Kenji Ohara
  • Kazuyuki Miyamoto
  • Hitoshi Hashimoto
  • Norihito Shintani
  • Akemichi Baba
  • Masaji Matsunaga
  • Seiji Shioda
Article

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional peptide that has been shown to be neuroprotective following a diverse range of cell injuries. Although several mechanisms regulating this effect have been reported, no direct evidence has linked PACAP to the regulation of oxidative stress, despite the fact that oxidative stress is a factor in the injury progression that occurs in most models. In the present study, we investigated the plasma oxidative metabolite and anti-oxidation potential levels of PACAP-deficient mice, as well as those of wild-type animals treated with PACAP38. These were assayed by the determination of Reactive Oxidative Metabolites (d-ROMs) and the Biological Anti-oxidant Potential (BAP) using the Free Radical Electron Evaluator system. We also investigated the direct radical scavenging potency of PACAP38 and the functional role of its receptor in the regulation of oxidative stress by PACAP, by using vasoactive intestinal peptide (VIP) and the PACAP receptor antagonist, PACAP6–38. Although younger PACAP null mice displayed no significant effect, greater d-ROMs and lower BAP values were recorded in older animals than in their wild-type littermates. Intravenous injection of PACAP38 in wild-type mice decreased the plasma d-ROMs and BAP values in a dose-dependent manner. These effects were not reproduced using VIP and were abolished by co-treatment with PACAP38 and the PAC1R antagonist PACAP6-38. Taken together, these results suggest that PACAP plays an important role in the physiological regulation of oxidative stress.

Keywords

PACAP PACAP-specific receptor (PAC1R) Oxidative stress Aging 

Notes

Acknowledgment

This work was supported in part by Research on Health Sciences focusing on Drug Innovation from The Japan Health Sciences Foundation (M.M. and S.S.). This study was also supported in part by a grant-in-aid from National Mutual Insurance Federation of Agricultural Cooperatives (K.D.).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Hirokazu Ohtaki
    • 1
  • Atsushi Satoh
    • 1
  • Tomoya Nakamachi
    • 1
  • Sachiko Yofu
    • 1
    • 2
  • Kenji Dohi
    • 1
  • Hiroyoshi Mori
    • 1
  • Kenji Ohara
    • 1
  • Kazuyuki Miyamoto
    • 1
  • Hitoshi Hashimoto
    • 3
  • Norihito Shintani
    • 3
  • Akemichi Baba
    • 3
  • Masaji Matsunaga
    • 2
  • Seiji Shioda
    • 1
  1. 1.Department of AnatomyShowa University School of MedicineTokyoJapan
  2. 2.Gene Trophology Research InstituteTokyoJapan
  3. 3.Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical SciencesOsaka UniversityOsakaJapan

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