NAD(P)H oxidase-induced oxidative stress in sympathetic ganglia of apolipoprotein E deficient mice.
Superoxide anion (O2*-) is increased throughout the arterial wall in atherosclerosis. The oxidative stress contributes to lesion formation and vascular dysfunction. In the present study, we tested the hypothesis that NAD(P)H oxidase-derived O2*- is increased in nodose sensory ganglia and sympathetic ganglia of apolipoprotein E deficient (apoE-/-) mice, an established animal model of atherosclerosis. O2*- measured ex vivo by L-012-enhanced chemiluminescence was increased by 79+/-17% in whole sympathetic ganglia from apoE-/- mice (n=5) compared with sympathetic ganglia from control mice (n=5) (P<0.05). In contrast, O2*- was not elevated in nodose ganglia from apoE-/- mice. Dihydroethidium staining confirmed the selective increase in O2*- in sympathetic ganglia of apoE-/- mice, and revealed the contribution of both neurons and non-neuronal cells to the O2*- generation. We investigated the enzymatic source of increased O2*- in sympathetic ganglia of apoE-/- mice. The mRNA expression of gp91phox, p22phox, p67phox, and p47phox subunits of NAD(P)H oxidase measured by real time RT-PCR was increased approximately 3-4 fold in sympathetic ganglia of apoE-/- mice (n=5) compared with control ganglia (n=5). NADPH oxidase activity measured by lucigenin chemiluminescence was increased by 68+/-12% in homogenates of sympathetic ganglia from apoE-/- mice (n=7) compared with control ganglia (n=7) (P<0.05). The results identify sympathetic ganglia as a novel site of oxidative stress in atherosclerosis, and suggest that upregulation of NAD(P)H oxidase is the source of increased O2*- generation. We speculate that oxidative stress in sympathetic ganglia may contribute to impaired baroreflex control of sympathetic nerve activity.
The Cardiovascular Center and Department of Internal Medicine, The University of Iowa, and The Veterans Affairs Medical Center, Iowa City, IA 52246, USA. xiuying-ma@uiowa.edu
Xiuying
X
Ma
Hannah J
HJ
Zhang
Carol A
CA
Whiteis
Xin
X
Tian
Robin L
RL
Davisson
Kevin C
KC
Kregel
Francois M
FM
Abboud
Mark W
MW
Chapleau
D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D004996:Ethidium / Q000031:analogs & derivatives; D005260:Female; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009620:Nodose Ganglion / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013481:Superoxides / Q000378:metabolism*
D001057:Apolipoproteins E; D021122:Protein Subunits; C067883:dihydroethidium; D013481:Superoxides; D019255:NADPH Oxidases; D004996:Ethidium