Superoxide production in nonatherosclerotic and atherosclerotic arteries
Expression of NAD(P)H oxidase subunits in nonatherosclerotic and atherosclerotic arteries
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Detection of intracellular production of reactive oxygen species.
A. Fluorescence microscopy visualization of ROS production in pericytes and smooth muscle cells. a: control;b: cells cultured in 25 mM glucose and AGE-Lys stimulated with Ang II;c and d : corresponding phase contrast microscopy. B. Pericytes cultured in the pro-diabetic environment, were loaded for 30 min at 37oC with 5mM DCF-DA .
Vascular effects of reactive oxygen species (ROS)
Modulation of cellular function by ROS in cardiovascular diseases
Potential role of NADPH oxidase in the pathogenesis of diabetic nephropathy
PKC-β inhibition suppresses diabetes-induced O2production
Redox-dependent signaling pathways by Ang II in vascular smooth muscle cells
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nonatherosclerotic arteries atherosclerotic arteries
In situ detection of superoxide in shamshamoperated and injured carotid arteries
Possible antioxidative agents for diabetic vascular complications
Initiation and amplification of the immune/inflammatory response by ROS-induced NFκ B activation in β-cell death
Schematic illustration of ROS-mediated NFκB activation
Mechanism for increased ROS production induced by diabetes and insulin-resistant state
Linking various risk factors to ROS generation in the development of IDDM
Elevated glucose and FFA levels contribute to the pathophysiology of diabetes via the generation of ROS
The role of serine kinase activation in oxidative stress induced insulin resistance
The effect of high glucose concentration, AGE-Lys AGEand their combination with Ang II on intracellular calcium [Ca2+]i
Detection of O2- production by dihydroethidium staining in mesangial cells overexpressing PKC-β2
Where and why are reactive oxygen species generated?
Mitochondria
– by-product of the oxidative metabolism
Phagocyte NADPH oxidase
– microbial killing
NADPH oxidase of non-phagocytic cells
Oxidative Stress and Diabetes
Jian Li
Beijing Institute of Geriatrics Ministry of Health
Redox "rheostat" in vascular cells
Reactive oxygen species (= ROS)
– cell growth, cell signaling
NOX-type NADPH oxidases
as superoxide-producing enzymes
O2
outside
H H115 H H
O2Fe
H
I
inside
V e
H
VI
FAD NH2 NADPH COOH
NADPH oxidase acidic pH, Superoxyde Dismutase (SOD)
O2
O2
Superoxide anion
H2 O2
Hydrogen peroxide
Proposed functions of ROS
killing of microorganisms DNA damage cancerogenesis ageing cell death NO inactivation and peroxynitrite generation regulation of cell growth and differentiation regulation of cell function oxygen sensing activation of redox-sensitive transcription factors activation of redox-sensitive second messenger systems
NAD(P)H Oxidase Activation
Adenovirus-induced overexpression of PKC-β2 causes the membranous translocation of p47phox and p67phox
A model illustrating how increased ROS production in accumulated fat contributes to metabolic syndrome
Review: Lambeth et al. Novel homologs of gp91phox.Trends in Biochemical Sciences 25: 459-461, 2000.
Structure of the NAD(P)H oxidase
Characteristics of neutrophil and vascular NAD(P)H oxidase
The NOX family of NADPH oxidases O O
2 2
EF-hands
eNADPH
gp91phox homology
Nox1 colon Nox2 phagocytes Nox3 inner ear Nox4 kidney Nox5 testis and lymphoid tissues
Effect of high glucose level and PMA on ROS production in aortic smooth muscle cells (A) and endothelial cells (B)
Effect of diphenylene iodonium on high glucose– or PMA-induced increase in ROS production in aortic smooth muscle cells (A) or endothelial cells (B)