Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone

被引:114
作者
Ding, YX
Chen, ZJ
Liu, SG
Che, DN
Vetter, M
Chang, CH
机构
[1] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA
[2] Univ Hosp Cleveland, Cleveland, OH 44106 USA
[3] Shandong Provincial Hosp, Reprod Res Ctr, Dept Med, Jinan, Peoples R China
关键词
D O I
10.1211/0022357055119
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
NAD(P)H oxiclase contributes to the pathogenesis of cancer and cardiovascular diseases such as hypertension, atherosclerosis, restenosis, cardiac hypertrophy and heart failure. Plumbagin, a plant-derived naphthoquinone, has been shown to exert anticarcinogenic and anti-atherosclerorsis effects in animals. However, the molecular mechanisms underlying these effects remain unknown. it. is possible that the beneficial effect of plumbagin is due to the inhibition of NAD(P)X oxidise. Human embryonic kidney 293 (HEK293) and brain tumour LN229 cells express mainly Nox-4, a renal NAD(P)H oxidase. We have examined the effect of plumbagin on Nox-4 activity in HEK293 and LN229 cells using lucigenin-dependent chemiluminescence assay. Plumbagin inhibited the activity or Nox-4 in a time- and dose-dependent manner in HEK293 and LN229 cells. Production or superoxide in HEK293 cells was inhibited by diphenyleneiodonium (DPI), a MAD(P)H oxiclase inhibitor. the superoxide production in HEK293 cells was NADPH- and NADH-dependent indicating that the superoxide was generated by a NAD(P)H oxiclase in HEK293 cells, but not by the redox-cycling or lucigenin. Furthermore, plumbagin inhibited the superoxide production in Nox-4 transfected COS-7 cells. These results indicated that plumbagin directly interacted with Nox-4 and inhibited its activity.
引用
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页码:111 / 116
页数:6
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共 38 条
[2]   OXIDANTS, ANTIOXIDANTS, AND THE DEGENERATIVE DISEASES OF AGING [J].
AMES, BN ;
SHIGENAGA, MK ;
HAGEN, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7915-7922
[3]   Two novel proteins activate superoxide generation by the NADPH oxidase NOX1 [J].
Bánfi, B ;
Clark, RA ;
Steger, K ;
Krause, KH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) :3510-3513
[4]   NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat [J].
Beswick, RA ;
Dorrance, AM ;
Leite, R ;
Webb, RC .
HYPERTENSION, 2001, 38 (05) :1107-1111
[5]   NADPH oxidases: not just for leukocytes anymore! [J].
Bokoch, GM ;
Knaus, UG .
TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (09) :502-508
[6]   The vascular NAD(P)H oxidases as therapeutic targets cardiovascular diseases [J].
Cai, H ;
Griendling, KK ;
Harrison, DG .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2003, 24 (09) :471-478
[7]   Reaction of reduced flavins and flavoproteins with diphenyliodonium chloride [J].
Chakraborty, S ;
Massey, V .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) :41507-41516
[8]   17β-estradiol inhibits soluble guanylate cyclase activity through a protein tyrosine phosphatase in PC12 cells [J].
Chen, ZJ ;
Che, DN ;
Vetter, M ;
Liu, SG ;
Chang, CH .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2001, 78 (05) :451-458
[9]   Molecular cloning of a regulatory protein for membrane bound guanylate cyclase GC-A [J].
Chen, ZJ ;
Miao, ZH ;
Vetter, M ;
Dulin, N ;
Liu, SG ;
Che, DN ;
Hughes, B ;
Murad, F ;
Douglas, J ;
Chang, CH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 278 (01) :106-111
[10]   Homologs of gp91phox:: cloning and tissue expression of Nox3, Nox4, and Nox5 [J].
Cheng, GJ ;
Cao, ZH ;
Xu, XX ;
Van Meir, EG ;
Lambeth, JD .
GENE, 2001, 269 (1-2) :131-140