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PMID: 9405639 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 26 ·1997-12-23 ·Pages 14483-8

Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT

Abstract

Superoxide anion (O2-) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated in the development of hypertension. In previous studies, we found that O2- is produced predominantly in the adventitia of isolated rabbit aorta and acts as a barrier to NO. In the present studies, we characterize the enzyme responsible for O2- production in the adventitia and show that this enzyme is a constitutively active NADPH oxidase with similar composition as the phagocyte NADPH oxidase. Constitutive O2--generating activity was localized to aortic adventitial fibroblasts and was enhanced by the potent vasoconstrictor angiotensin II. Immunohistochemistry of aortic sections demonstrated the presence of p22(phox), gp91(phox), p47(phox), and p67(phox) localized exclusively in rabbit aortic adventitia, coincident with the site of staining for O2- production. Furthermore, immunodepletion of p67(phox) from adventitial fibroblast particulates resulted in the loss of NADPH oxidase activity, which could be restored by the addition of recombinant p67(phox). Further study into the regulation of this adventitial source of O2- is important in elucidating the mechanisms regulating the bioactivity of NO and may contribute to our understanding of the pathogenesis of hypertension.

MeSH Terms
Angiotensin II/pharmacology Animals Aorta/cytology,metabolism Cells, Cultured Immunohistochemistry Membrane Transport Proteins NADPH Dehydrogenase/metabolism NADPH Oxidases/metabolism Phagocytes/metabolism Phosphoproteins/metabolism Rabbits Vasoconstrictor Agents/pharmacology
Chemicals
Membrane Transport Proteins Phosphoproteins Vasoconstrictor Agents neutrophil cytosol factor 67K Angiotensin II NADPH Oxidases CYBA protein, human NADPH Dehydrogenase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pagano P J
Vascular Biology Unit, Boston Medical Center, Boston, MA 02118, USA. [email protected]
Clark J K
Cifuentes-Pagano M E
Clark S M
Callis G M
Quinn M T
References (48)
48 references, click to expand
  1. Antioxidant therapy partially blocks immune-induced lung fibrosis.
    Inflammation. 1995 Apr;19(2):207-19 PMID: 7601506
  2. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation.
    J Clin Invest. 1995 Jun;95(6):2520-9 PMID: 7769097
  3. Topological mapping of neutrophil cytochrome b epitopes with phage-display libraries.
    J Biol Chem. 1995 Jul 14;270(28):16974-80 PMID: 7622517
  4. Angiotensin II-induced cardiac fibrosis in the rat is increased by chronic inhibition of nitric oxide synthase.
    J Clin Invest. 1995 Nov;96(5):2469-77 PMID: 7593636
  5. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.
    J Clin Invest. 1996 Apr 15;97(8):1916-23 PMID: 8621776
  6. NADPH oxidase of neutrophils.
    Biochim Biophys Acta. 1996 Feb 15;1273(2):87-107 PMID: 8611594
  7. Salicylate or aspirin inhibits the induction of the inducible nitric oxide synthase in rat cardiac fibroblasts.
    Circ Res. 1996 May;78(5):759-68 PMID: 8620595
  8. Myofibroblasts differentiate from fibroblasts when plated at low density.
    Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4219-23 PMID: 8633044
  9. Vitamin E reduces bleomycin-induced lung fibrosis in mice: biochemical and morphological studies.
    J Basic Clin Physiol Pharmacol. 1993 Jul-Sep;4(3):249-69 PMID: 8679519
  10. Assembly of the human neutrophil NADPH oxidase involves binding of p67phox and flavocytochrome b to a common functional domain in p47phox.
    J Biol Chem. 1996 Jul 19;271(29):17013-20 PMID: 8663333
  11. Inhibition of NO-medicate responses by 7-ethoxyresorufin, a substrate and competitive inhibitor of cytochrome P450.
    Br J Pharmacol. 1996 May;118(1):57-62 PMID: 8733576
  12. Effects of angiotensin II infusion and inhibition of nitric oxide synthase on the rat aorta.
    Hypertension. 1996 Aug;28(2):153-8 PMID: 8707375
  13. Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
    J Clin Invest. 1996 Jul 15;98(2):345-51 PMID: 8755643
  14. Angiotensin and bradykinin metabolism by peptidases identified in cultured human skeletal muscle myocytes and fibroblasts.
    Peptides. 1995;16(8):1367-73 PMID: 8745045
  15. Inhibition of relaxations to nitrergic stimulation of the mouse anococcygeus by duroquinone.
    Br J Pharmacol. 1995 Dec;116(8):3231-6 PMID: 8719801
  16. Chronic control of high blood pressure in the spontaneously hypertensive rat by delivery of angiotensin type 1 receptor antisense.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9960-5 PMID: 8790439
  17. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells.
    J Biol Chem. 1996 Sep 20;271(38):23317-21 PMID: 8798532
  18. Genomic structure, chromosomal localization, start of transcription, and tissue expression of the human p40-phox, a new component of the nicotinamide adenine dinucleotide phosphate-oxidase complex.
    Blood. 1996 Oct 1;88(7):2714-21 PMID: 8839867
  19. Expression of phagocyte NADPH oxidase components in human endothelial cells.
    Am J Physiol. 1996 Oct;271(4 Pt 2):H1626-34 PMID: 8897960
  20. Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins.
    J Leukoc Biol. 1996 Dec;60(6):677-91 PMID: 8975869
  21. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation.
    Immunity. 1996 Dec;5(6):653-66 PMID: 8986723
  22. Lucigenin (bis-N-methylacridinium) as a mediator of superoxide anion production.
    Arch Biochem Biophys. 1997 Jan 1;337(1):115-20 PMID: 8990275
  23. Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension.
    Circulation. 1997 Feb 4;95(3):588-93 PMID: 9024144
  24. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts.
    Science. 1997 Mar 14;275(5306):1649-52 PMID: 9054359
  25. Functional expression of NADPH oxidase components (alpha- and beta-subunits of cytochrome b558 and 45-kDa flavoprotein) by intrinsic human glomerular mesangial cells.
    J Biol Chem. 1991 Nov 5;266(31):21025-9 PMID: 1657945
  26. Modulation of fibroblast proliferation by oxygen free radicals.
    Biochem J. 1990 Feb 1;265(3):659-65 PMID: 2154966
  27. The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages.
    J Immunol Methods. 1990 Oct 19;133(2):175-9 PMID: 2121828
  28. Release of intact endothelium-derived relaxing factor depends on endothelial superoxide dismutase activity.
    Am J Physiol. 1991 Feb;260(2 Pt 1):C219-25 PMID: 1847583
  29. Increased type I collagen mRNA levels in cultured scleroderma fibroblasts.
    Biochim Biophys Acta. 1984 Feb 24;781(1-2):183-6 PMID: 6696914
  30. Differences and similarities between human and rabbit neutrophil granulocyte responses in vitro: the effects of zymosan-activated plasma, phorbol myristate acetate and n-formyl-methionyl-leucyl-phenylalanine.
    Acta Anaesthesiol Scand. 1987 Aug;31(6):491-8 PMID: 3630594
  31. Indications to an NADPH oxidase as a possible pO2 sensor in the rat carotid body.
    FEBS Lett. 1989 Oct 9;256(1-2):75-8 PMID: 2806553
  32. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2.
    Science. 1991 Dec 6;254(5037):1512-5 PMID: 1660188
  33. Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression.
    Circ Res. 1992 Mar;70(3):593-9 PMID: 1371430
  34. Stabilization of human neutrophil NADPH oxidase activated in a cell-free system by cytosolic proteins and by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide.
    J Biol Chem. 1992 Apr 15;267(11):7529-38 PMID: 1313806
  35. Identification of a thermolabile component of the human neutrophil NADPH oxidase. A model for chronic granulomatous disease caused by deficiency of the p67-phox cytosolic component.
    J Clin Invest. 1992 May;89(5):1587-95 PMID: 1314852
  36. Differential gene expression and regulation of type-1 angiotensin II receptor subtypes in the rat.
    Biochem Biophys Res Commun. 1992 Oct 15;188(1):446-52 PMID: 1384488
  37. The cytochrome b-558 molecules involved in the fibroblast and polymorphonuclear leucocyte superoxide-generating NADPH oxidase systems are structurally and genetically distinct.
    Biochem J. 1993 Jan 15;289 ( Pt 2):481-6 PMID: 7678734
  38. Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release: role of protein kinase C.
    Nucleic Acids Res. 1993 Mar 11;21(5):1259-63 PMID: 8464709
  39. Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11880-4 PMID: 8265642
  40. Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits.
    J Clin Invest. 1994 Feb;93(2):844-51 PMID: 8113416
  41. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.
    Circ Res. 1994 Jun;74(6):1141-8 PMID: 8187280
  42. NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium.
    Am J Physiol. 1994 Jun;266(6 Pt 2):H2568-72 PMID: 8024019
  43. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway.
    J Clin Invest. 1994 Aug;94(2):771-8 PMID: 8040332
  44. The adventitia may be a barrier specific to nitric oxide in rabbit pulmonary artery.
    J Clin Invest. 1994 Nov;94(5):1883-8 PMID: 7962533
  45. Sites of superoxide anion production detected by lucigenin in calf pulmonary artery smooth muscle.
    Am J Physiol. 1994 Dec;267(6 Pt 1):L815-22 PMID: 7810685
  46. Aminopeptidase N: a constitutive cell-surface protein on human dermal fibroblasts.
    Cell Immunol. 1995 Apr 15;162(1):42-8 PMID: 7704909
  47. The formation and biologic significance of phagocyte-derived oxidants.
    J Investig Med. 1995 Feb;43(1):39-49 PMID: 7719758
  48. An NADPH oxidase superoxide-generating system in the rabbit aorta.
    Am J Physiol. 1995 Jun;268(6 Pt 2):H2274-80 PMID: 7611477
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.26.14483
Email
[email protected]
Published
1997-12-23
Pages
14483-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25029
Subset
IM
Grants
NIAMS NIH HHS · R01 AR042426 · United States
NHLBI NIH HHS · R01 HL055425 · United States
NIAMS NIH HHS · R01 (AR42426) · United States
NHLBI NIH HHS · R29 HL55425-02 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.26.14483 PMC Full Text View journal details
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