Peroxide inactivates calcium pumps in pig coronary artery

Grover, Ashok K.; Samson, Sue E.; Fomin, Victor P.

doi:10.1152/ajpheart.1992.263.2.h537

Cited by 56 publications

(44 citation statements)

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“…Removal of extracellular Ca 2ϩ or administration of Ca 2ϩ channel blockers markedly reduces the contraction induced by exogenous ROS (3,48). In addition, ROS release Ca 2ϩ from intracellular stores by inhibiting Ca 2ϩ -ATPase activity and promoting inositol triphosphate-induced Ca 2ϩ release (13,14). Increases in intracellular Ca 2ϩ levels result in activation of proteins including PKC and Ca 2ϩ -dependent calmodulin kinases, leading to smooth muscle contraction.…”

Section: Discussionmentioning

confidence: 99%

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Jin

Zhao

Webb

2004

American Journal of Physiology-Heart and Circulatory Physiology

225

185

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. Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. Am J Physiol Heart Circ Physiol 287: H1495-H1500; 2004; 10.1152/ajpheart.01006.2003.-Evidence indicates that both the Rho/ Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H 2O2 are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 M) significantly reduced X/XOinduced contraction. A Rho kinase inhibitor, (ϩ)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca 2ϩ -independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca 2ϩ sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca 2ϩ -independent PKC. myosin light chain phosphatase; smooth muscle contraction; antioxidants CONTRACTION OF SMOOTH MUSCLE is regulated by both Ca 2ϩ -dependent and Ca 2ϩ -independent (Ca 2ϩ sensitization) mechanisms. A rise in intracellular Ca 2ϩ levels leads to myosin light chain (MLC) kinase activation, resulting in an increase in MLC phosphorylation. Importantly, MLC phosphorylation can also be increased through inhibition of MLC phosphatase, which augments smooth muscle force generation without a change in intracellular Ca 2ϩ (38).In recent years, studies have revealed that the small GTPase Rho and its downstream target Rho kinase mediate the Ca 2ϩ sensitization of smooth muscle contraction (37). The exchange of bound GDP for GTP activates Rho and stimulates its translocation from cytosol to membrane. Rho-GTP phosphorylates Rho kinase, which inhibits MLC phosphatase activity by phosphorylation of the MLC phosphatase target subunit (MYPT1). A decrease in MLC phosphatase activity increases phosphorylation of myosin and therefore contributes to smooth muscle contraction at low levels of intracellular Ca 2ϩ concentration. Strong evidence suggests that increased Rho/Rho kinase-dependent Ca 2ϩ sensitization contributes to hypertension and inhibition of Rho or Rho kinase reduces blood pressure (33, 42). Some heterotrimetric G protein-coupled receptor (GPCR) agonists, including angiotensin II (ANG II) and endothelin (ET)-1, induce smooth mus...

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Section: Discussionmentioning

confidence: 99%

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Jin

Zhao

Webb

2004

American Journal of Physiology-Heart and Circulatory Physiology

225

185

View full text Add to dashboard Cite

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“…Under oxidative stress, reactive oxygen and nitrogen can disrupt normal physiological pathways and cause cell death via altered Ca 2ϩ homeostasis (7,30 (14,15). It seems that SERCA can be inhibited both by oxidation of its sulfhydryl residues and by a direct attack of oxidants on the ATP-binding site (7).…”

Section: Discussionmentioning

confidence: 99%

Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide

Ihara

Urata²,

Goto³

et al. 2006

American Journal of Physiology-Cell Physiology

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“…21 Rather, SERCA2, which is the primary isoform in vascular smooth muscle, is sensitive to oxidative stress. 26 For example, hydroxyl radical, 27 peroxide, 28 hypochlorous acid, 29 and peroxynitrite 30 all decrease SERCA activity. Therefore, SERCA activity and NO-induced relaxation might be impaired by oxidative stress in HC.…”

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confidence: 99%

Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca ²⁺ -ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation

Adachi

Matsui

et al. 2002

Circulation Research

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Abstract-Antioxidants improve endothelial function in hypercholesterolemia (HC); however, whether this includes improvement of the vascular smooth muscle response to NO is unknown. NO relaxes arteries, in part, by stimulating Ca 2ϩ uptake via sarco/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA) in aortic smooth muscle, and HC impairs SERCA function and the response to NO. HC induces oxidative stress, which could impair SERCA function. To study the effect of antioxidants, which are known to improve endothelium-dependent relaxation in HC, smooth muscle SERCA activity and NO-induced relaxation were studied in rabbits fed normal chow or a 0.5% cholesterol diet for 13 weeks. The antioxidant t-butylhydroxytoluene (BHT, 1%) was mixed with the HC diet in the last 3 weeks. HC impaired acetylcholine-and NO-induced relaxation, and these were restored by BHT. After inhibiting SERCA with thapsigargin, no difference existed in NO-induced relaxation among the three groups. Reduced aortic SERCA activity in HC was restored by BHT without changing SERCA protein expression. 3-Nitrotyrosine was notably increased in the media of the HC aorta, where it colocalized with SERCA. Tyrosine-nitrated SERCA protein was immunoprecipitated in the aortas of HC rabbits, where it was decreased by BHT, and it was also detected in the aortas of atherosclerotic humans. Thus, the antioxidant reverses impaired smooth muscle SERCA function in HC, and this is correlated with the improved relaxation to NO. These beneficial effects may depend on reducing the direct effects on SERCA of reactive oxygen species that are augmented in HC. Key Words: t-butylhydroxytoluene Ⅲ nitric oxide Ⅲ sarco/endoplasmic reticulum Ca 2ϩ -ATPase Ⅲ atherosclerosis Ⅲ nitrotyrosine H ypercholesterolemia (HC) and other vascular diseases, including hypertension, 1-3 diabetes, 4,5 and hyperhomocysteinemia, 6,7 may increase oxidative stress and decrease NO bioactivity, which may be associated with promoting atherosclerosis. 8 Antioxidants, including ␤-carotine, 9 vitamin E, 9,10 vitamin C, 11 and probucol, 12,13 improve endotheliumdependent relaxation in HC. The effects of these antioxidants do not depend on lowering plasma cholesterol levels, 12,13 suggesting that oxidative stress in HC is related to vascular dysfunction. 14 However, the protective mechanism of antioxidants on NO bioactivity has not yet been elucidated.Oxidative stress may impair NO release 15 or endothelial NO synthase function, 16 although increased NO release in HC has also been reported. 17 Increased scavenging of NO by superoxide may decrease NO bioactivity; however, a few hours of incubation with antioxidants 18,19 or adenovirusmediated gene transfer of superoxide dismutase 20 fails to normalize endothelium-dependent relaxation, suggesting that a decrease in superoxide generation is not enough to immediately restore NO bioactivity in HC.Another possible factor is that oxidative stress impairs the function of target proteins of NO in aortic smooth muscle. NO activates guanylyl cyclase and relaxes arteries, and its...

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Peroxide inactivates calcium pumps in pig coronary artery

Cited by 56 publications

References 0 publications

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide

Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca ²⁺ -ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation

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Peroxide inactivates calcium pumps in pig coronary artery

Cited by 56 publications

References 0 publications

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide

Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca 2+ -ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation

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Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca ²⁺ -ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation