title: Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor.
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.
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satoh
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yofu
authors.forename: Kenji
authors.initials: K
authors.lastname: Dohi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Masaji
authors.initials: M
authors.lastname: Matsunaga
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000097:blood; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017382:Reactive Oxygen Species; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
references.citation: Regul Pept. 2004 Dec 15;123(1-3):61-7
references.pmid: 15518894
references.citation: Neurosci Res. 2007 Aug;58(4):349-55
references.pmid: 17628732
references.citation: Circ J. 2010 Jun;74(6):1183-90
references.pmid: 20378996
references.citation: Jpn J Physiol. 1998 Oct;48(5):301-31
references.pmid: 9852340
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):1053-8
references.pmid: 11792830
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7488-93
references.pmid: 16651528
references.citation: Peptides. 2006 Jan;27(1):87-94
references.pmid: 16095757
references.citation: J Clin Biochem Nutr. 2010 Mar;46(2):93-104
references.pmid: 20216941
references.citation: Ageing Res Rev. 2009 Jul;8(3):199-213
references.pmid: 19427410
references.citation: Regul Pept. 2004 Dec 15;123(1-3):51-9
references.pmid: 15518893
references.citation: Brain Res. 1996 Oct 14;736(1-2):280-6
references.pmid: 8930334
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):61-72
references.pmid: 18491044
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):16-25
references.pmid: 18483879
references.citation: Neuroimmunomodulation. 2002-2003;10(3):177-86
references.pmid: 12481158
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:75-89
references.pmid: 16888150
references.citation: J Comp Neurol. 2002 Jun 24;448(2):203-16
references.pmid: 12012430
references.citation: Arch Physiol Biochem. 2001 Oct;109(4):377-82
references.pmid: 11935377
references.citation: Biochem Biophys Res Commun. 1989 Oct 16;164(1):567-74
references.pmid: 2803320
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13355-60
references.pmid: 11687615
references.citation: Pharmacol Rev. 2000 Jun;52(2):269-324
references.pmid: 10835102
references.citation: Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):115-23
references.pmid: 17270184
references.citation: Blood. 2006 Jan 15;107(2):661-8
references.pmid: 16204306
references.citation: Lung. 2001;179(1):1-8
references.pmid: 11479689
references.citation: Peptides. 2010 Apr;31(4):592-602
references.pmid: 20034524
references.citation: Peptides. 2005 Dec;26(12):2518-24
references.pmid: 16009465
references.citation: Regul Pept. 2010 Feb 25;160(1-3):91-8
references.pmid: 19969027
references.citation: Neurosci Lett. 2010 Jan 18;469(1):70-4
references.pmid: 19932736
references.citation: Stroke. 2000 Jun;31(6):1411-7
references.pmid: 10835464
references.citation: Neurosci Res. 2003 Mar;45(3):313-24
references.pmid: 12631467
references.citation: J Neurosci. 1999 May 1;19(9):3414-22
references.pmid: 10212301
references.citation: Free Radic Res. 2006 Dec;40(12):1339-49
references.pmid: 17090423
references.citation: Eur J Endocrinol. 2009 Apr;160(4):561-5
references.pmid: 19174531
references.citation: Stroke. 1999 Sep;30(9):1962-8
references.pmid: 10471451
references.citation: Eur J Pharmacol. 2006 Mar 8;533(1-3):182-94
references.pmid: 16473346
references.citation: Eur J Neurosci. 2002 May;15(9):1451-60
references.pmid: 12028355
references.citation: Crit Rev Oral Biol Med. 2002;13(3):229-37
references.pmid: 12090463
references.citation: Pulm Pharmacol Ther. 1999;12(4):229-36
references.pmid: 10500002
references.citation: Neurochem Res. 2009 Apr;34(4):679-87
references.pmid: 18688709
references.citation: J Neurochem. 2006 Jul;98(2):321-9
references.pmid: 16805827