Direct and Indirect Roles of Cytochrome b in the Mediation of Superoxide Generation and NO Catabolism by Mitochondrial Succinate-Cytochrome c Reductase

Chen, Yeong Renn; Chen, Chwen Lih; Yeh, Alexander; Li, Xiaoping; Zweíer, Jay L.

doi:10.1074/jbc.m513627200

Cited by 43 publications

(39 citation statements)

References 48 publications

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“…This is probably because shear exposure inhibits complex I and III activities by ϳ80 and ϳ70%, respectively , and, at least in the case of complex III, decreased complex activity reduces the enzyme-mediated O 2 . production (Chen et al, 2006). L-NAME did not affect the fluorescence signal in static ECs but significantly inhibited the increase in fluorescence in sheared ECs, suggesting NO involvement in the shear-induced mitochondrial O 2 .…”

Section: No and Ros Arementioning

confidence: 99%

Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial Cells

Han

Varadharaj

Giedt

et al. 2009

J Pharmacol Exp Ther

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Bovine aortic endothelial cells (ECs) respond to nitric oxide (NO) donors by activating the redox-sensitive NF-E2-related factor 2/antioxidant response element pathway and up-regulating heme oxygenase (HO)-1 expression. EC exposure to steady laminar shear stress causes a sustained increase in NO, a transient increase in reactive oxygen species (ROS), and activation of the HO-1 gene. Because steady laminar flow increases the mitochondrial superoxide (O 2 . ) production, we hypothesized that mitochondria-derived ROS play a role in shear-induced HO-1 expression. Flow (10 dynes/cm 2 , 6 h)-induced expression of HO-1 protein was abolished when BAECs were preincubated and sheared in the presence of either N G -nitro-L-arginine methyl ester or N-acetyl-L-cysteine, suggesting that either NO or ROS up-regulates HO-1. Ebselen and diphenylene iodonium blocked HO-1 expression, and uric acid had no effect. The mitochondrial electron transport chain inhibitors, myxothiazol, rotenone, or antimycin A, and the mi- The stress proteins heme oxygenases, which consist of constitutive and inducible isozymes (HO-2 and HO-1, respectively), catalyze the rate-limiting step in the degradation of heme to the bile pigments, biliverdin and bilirubin, eventually releasing iron and carbon monoxide. Because the HO reaction products are known to provide cytoprotection from inflammatory diseases, including atherosclerosis, mechanisms of HO-1 induction have been studied extensively (Ryter et al., 2006). HO-1 is induced by chemicals that produce oxidative stress. The signaling pathways leading to the transcriptional regulation of the HO-1 gene are variable in a celland inducer-specific fashion, although all of them involve the

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Section: No and Ros Arementioning

confidence: 99%

Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial Cells

Han

Varadharaj

Giedt

et al. 2009

J Pharmacol Exp Ther

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“…The role of O 2 . in initiation of mitochondrial dysfunction also has been further demonstrated by electron paramagnetic resonance spin-trapping studies using 5-diethoxylphosphoryl-5-methyl-1-pyrroline N-oxide using isolated complex II/ III and superoxide dismutase (Chen et al, 2006(Chen et al, , 2007. Immunoblotting analysis of myocardial tissue homogenates with antibodies (anti-51 kDa) against the FMN-binding subunit of complex I, antibodies (anti-70 kDa) against the FAD-binding subunit of complex II, and antibodies (antiCoXI and anti-CoXVb) against the subunits I and Vb of complex IV, indicates that marked up-regulation of mitochondrial protein expression occurs in the postischemic heart pretreated with DMPO (Fig.…”

Section: Downloaded Frommentioning

confidence: 99%

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Zuo¹,

Chen²,

Reyes³

et al. 2009

J Pharmacol Exp Ther

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Free radicals are important mediators of myocardial ischemiareperfusion injury. Nitrone spin traps have been shown to scavenge free radicals. The cardioprotective effect of the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was investigated in an isolated heart model of global ischemia and reperfusion. Rat hearts were perfused and subjected to global ischemia for 30 min followed by reperfusion with four treatment groups of varying DMPO concentration (0.5-10 mM) administered before induction of ischemia. DMPO treatment improved the recovery of left ventricular (LV) function and coronary flow over the 30-min period of reperfusion compared with untreated hearts. Enhanced recovery was observed for all doses studied but was highest with 1 mM treatment with 2.4-fold higher recovery of LV developed pressure and 37% reduction in infarct size. Superoxide was measured by tissue fluorometry using the O 2 . probe hydroethidine. Hearts treated with 1 mM DMPO showed a significant reduction in O 2 . production compared with control hearts both over the first 5 min of ischemia and upon reperfusion after 30 min of global ischemia. Studies of mitochondrial function demonstrated that 1 mM DMPO increased the

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“…5, A and B). However, it significantly blocked the shear-induced increase in fluorescence, possibly because shear exposure inhibits complex III activity by ϳ70% (30) and decreased complex III activity reduces the enzyme-mediated O 2 ⅐ Ϫ production (14). Last, when either static or sheared ECs were treated with both L-NAME and antimycin A, the signal was significantly increased compared with either static or sheared ECs treated with just L-NAME, respectively, suggesting that MitoSOX fluorescence of ECs in the absence of NO is sensitive to O 2 ⅐ Ϫ generation by the ETC complex III (Fig.…”

Section: Mitochondrial O 2 ⅐ ϫ Production By Sheared Ecs Increases Wimentioning

confidence: 99%

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Jones¹,

Han²,

Presley³

et al. 2008

American Journal of Physiology-Cell Physiology

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Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO Ϫ ) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O2, compared with more physiological O2 tensions (PO2), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O2 ⅐ Ϫ ) generation leading to ONOO Ϫ formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2 consumption rates of bovine aortic ECs sheared (10 dyn/cm 2 , 30 min) at 5%, 10%, or 21% O2 or left static at 5% or 21% O2. Respiration was inhibited to a greater extent when ECs were sheared at 21% O2 than at lower PO2 or left static at different PO2. Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO Ϫ scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O2 ⅐ Ϫ production was higher in ECs sheared at 21% than at 5% O2, as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O2 was modestly increased compared with ECs sheared at lower PO2, suggesting that eNOS activity may be higher at 21% O2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2 ⅐ Ϫ production, leads to enhanced ONOO Ϫ formation intramitochondrially and suppression of respiration. shear stress; endothelium; mitochondria; reactive oxygen species MITOCHONDRIA ARE THE SUBCELLULAR organelles for the production of cellular energy, but they also activate intracellular signaling pathways that modulate cell proliferation or promote cell cycle arrest and apoptosis by oxidative or nitrosative reactions. These reactions are regulated by the matrix concentration of nitric oxide (NO), which diffuses to the mitochondria from the cytosolic NO synthase (NOS) isoforms and is thought to be produced also locally by a mitochondrial NOS variant (11). In rat heart, skeletal muscle and liver mitochondria (15,57,58), isolated rat hearts (59), and whole animals (68), NO at physiological concentrations binds reversibly and in competition with oxygen (O 2 ) to the reduced binuclear center Cu B /a 3 of cytochrome-c oxidase (complex IV) of the electron transport chain (ETC) and inhibits mitochondrial O 2 uptake. At slightly higher concentrations, NO oxidizes ubiquinol of ubiquinolcytochrome c reductase (complex III) to increase unstable ubisemiquinone, which, by univalent electron transfer to O 2 , produces the reactive O 2 species (ROS) superoxide (O 2 ⅐ Ϫ ) (57, 58). O 2 ⅐ Ϫ generated from that location is released both into the matrix and intermembrane space (51), where it is dismutated to hydrogen peroxide (H 2 O 2 ) by manganese superoxide dismutase (MnSOD) and copper zinc SOD (CuZ...

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Direct and Indirect Roles of Cytochrome b in the Mediation of Superoxide Generation and NO Catabolism by Mitochondrial Succinate-Cytochrome c Reductase

Cited by 43 publications

References 48 publications

Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial Cells

Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial Cells

The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

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