Redox Regulation of Signal Transduction in Cardiac and Smooth Muscle

Suzuki, Yuichiro; Ford, George D.

doi:10.1006/jmcc.1998.0872

Cited by 159 publications

(106 citation statements)

References 5 publications

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“…For example, because H 2 O 2 is a nonpolar and nonradical molecule, it is membrane-permeable and diffusible, less reactive, and longer lived than other ROS. These characteristics of H 2 O 2 make it function as an efficient signaling molecule (22)(23)(24)(25) (2). Therefore, the intracellular defense mechanism for maintaining a constant intracellular H 2 O 2 concentration is an important factor in deciding whether to go to cell growth or death.…”

Section: Discussionmentioning

confidence: 99%

Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2*

Baek

Han

Sung

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2*

Baek

Han

Sung

et al. 2012

Journal of Biological Chemistry

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“…Apart from a well-established role in pulmonary vascular disease, there is now irrefutable evidence that endogenous ROS also act in physiological roles as intracellular second messengers (8,60,61) to enable basic cellular processes such as proliferation. This raises the concern that systemically administered broad spectrum antioxidant interventions, designed to prevent oxidant-mediated injury, could also arrest signals for normal growth in the neonate.…”

Section: Discussionmentioning

confidence: 99%

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

Jankov¹,

Kantores²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

117

105

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Jankov RP, Kantores C, Pan J, Belik J. Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats. Am J Physiol Lung Cell Mol Physiol 294: L233-L245, 2008. First published December 14, 2007 doi:10.1152/ajplung.00166.2007.-Xanthine oxidase (XO)-derived reactive oxygen species (ROS) formation contributes to experimental chronic hypoxic pulmonary hypertension in adults, but its role in neonatal pulmonary hypertension has received little attention. In rats chronically exposed to hypoxia (13% O2) for 14 days from birth, we examined the effects of ROS scavengers (U74389G 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 or Tempol 100 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ip) or a XO inhibitor, Allopurinol (50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ip). Both ROS scavengers limited oxidative stress in the lung and attenuated hypoxia-induced vascular remodeling, confirming a critical role for ROS in this model. However, both interventions also significantly inhibited somatic growth and normal cellular proliferation in distal air spaces. Hypoxiaexposed pups had evidence of increased serum and lung XO activity, increased vascular XO-derived superoxide production, and vascular nitrotyrosine formation. These changes were all prevented by treatment with Allopurinol, which also attenuated hypoxia-induced vascular remodeling and partially reversed inhibited endothelium-dependent arterial relaxation, without affecting normal growth and proliferation. Collectively, our findings suggest that XO-derived superoxide induces endothelial dysfunction, thus impairing pulmonary arterial relaxation, and contributes to vascular remodeling in hypoxia-exposed neonatal rats. Due to the potential for adverse effects on normal growth, targeting XO may represent a superior "antioxidant" strategy to ROS scavengers for neonates with pulmonary hypertension.antioxidants; allopurinol; U74389G; Tempol; 8-isoprostane PULMONARY HYPERTENSION (PHT) is a common condition of the critically ill neonate (12,18,52,64,65). An increased propensity to PHT in the newborn period, compared with other stages of life, is predominantly related to two factors: a failure in the physiological fall in pulmonary vascular resistance required for a successful transition to postnatal life, and the rapid development of anatomical changes in the heart and pulmonary vasculature (23), known collectively as vascular remodeling. Evidence suggests that abnormally decreased pulmonary arterial relaxation is an early functional feature of PHT that directly contributes to the subsequent anatomical changes of remodeling (1). Together, these changes lead to narrowing of the vessel lumen, exaggerated responses to constrictors (3,14), and reduced compliance, all of which are believed to contribute to a chronic and progressive form of PHT that is refractory to current therapies (13).A major pathological role for increased generation of reactive oxygen species (ROS) in the pathogenesis of experimental PHT is evidenced by antioxidant intervention studies performed in fetal lambs (24, 39), in hyperoxia-exp...

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“…There is increasing evidence that NAD(P)H oxidase is a major source of O 2 .− in the vasculature and that O 2 .− from this enzyme serves as an important physiological redox signaling molecule to participate in the regulation of vascular function [1,[25][26][27][28]. In vascular smooth muscle cells (VSMCs), recent studies have reported that there are membrane-bound and intracellular nonmitochondrial NAD(P)H oxidases, which are all capable of producing O 2 .− and contributing to intracellular O 2 .− concentrations in these cells [1,29].…”

Section: Discussionmentioning

confidence: 99%

“…However, accumulating evidence has indicated that non-mitochondrial NAD(P)H oxidase may be a major resource for intracellular ROS in vascular smooth muscle cells and thereby this enzyme system play an important role in the regulation of vascular smooth muscle function under physiological and pathological conditions [1,[25][26][27][28]. In this regard, previous studies have reported that Nox4 is a major catalytic subunit of NAD(P)H oxidase in different organelle of vascular smooth muscle cells including the SR [3,7,24].…”

Section: Discussionmentioning

confidence: 99%

Local production of O2− by NAD(P)H oxidase in the sarcoplasmic reticulum of coronary arterial myocytes: cADPR-mediated Ca2+ regulation

Zhang

Jin

Xia

et al. 2008

Cellular Signalling

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The present study was designed to determine whether the sarcoplasmic reticulum (SR) could locally produce superoxide (O 2 .− ) via NAD(P)H oxidase (NOX) in coronary arterial myocytes (CAMs) and to address whether cADPR-RyR/Ca 2+ signaling pathway regulates this local O 2 .− production from the SR. Using confocal microscopic imaging analysis in intact single CAMs, a cell-permeable indicator CM-H 2 DCFDA for dynamic changes in intracellular ROS (in green color) and a highly selective ER-Tracker ™ Red dye for tracking of the SR were found co-localized. A quantitative analysis based on the intensity of different spectra demonstrated a local O 2 .− production derived from the SR. M 1 -receptor agonist, oxotremorine (Oxo) and a Ca 2+ ionophore, A23187 time-dependently increased this O 2 .− production colocalized with the SR. NOX inhibitors, diphenylene iodonium (DPI) and apocynin (Apo), or superoxide dismutase (SOD) and catalase, and Nox4 (a major intracellular NOX subunit) siRNA all substantially blocked this local production of O 2 .− , demonstrating an involvement of NOX. This SR-derived O 2 .− production was also abolished by the inhibitors of cyclic ADP-ribose (cADPR)-mediated Ca 2+ signaling, such as nicotinamide (Nicot, 6 mM), ryanodine (Rya, 50 μM) or 8-Br-cADPR (30 μM). However, IP 3 antagonist, 2-APB (50 μM) had no effect. In CAMs transfected with siRNA of ADP-ribosyl cyclase or RyR, this SR O 2 .− production was attenuated. Electron spin resonance (ESR) spectromic assay in purified SR also demonstrated the production of O 2 .− that was dependent on NOX activity and Ca 2+ concentrations. These results provide direct evidence that O 2 .− could be locally produced via NOX on the SR and that this local O 2 .− producing system is controlled by cADPR-RyR/Ca 2+ signaling pathway.

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Redox Regulation of Signal Transduction in Cardiac and Smooth Muscle

Cited by 159 publications

References 5 publications

Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2*

Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2*

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

Local production of O2− by NAD(P)H oxidase in the sarcoplasmic reticulum of coronary arterial myocytes: cADPR-mediated Ca2+ regulation

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