P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction.

Abstract:

:The p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production. RNAi-mediated down-regulation of endogenous p66shc led to activation of the proto-oncogene ras, and Akt kinase, with a corresponding increase in phosphorylation of eNOS at S1177 (S1179 on bovine eNOS). In rat aortic rings, down-regulation of p66shc suppressed the vasoconstrictor response to phenyephrine that was abrogated by treatment with the NOS inhibitor l-NAME, and enhanced vasodilation induced by sub-maximal doses of acetylcholine. These findings highlight a pivotal role for p66shc in inhibiting endothelial NO production, and endothelium-dependent vasorelaxation, that may provide important mechanistic information about endothelial dysfunction seen with aging.

journal_name

J Mol Cell Cardiol

authors

Yamamori T,White AR,Mattagajasingh I,Khanday FA,Haile A,Qi B,Jeon BH,Bugayenko A,Kasuno K,Berkowitz DE,Irani K

doi

10.1016/j.yjmcc.2005.09.003

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

992-5

issue

6

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(05)00282-8

journal_volume

39

pub_type

杂志文章
  • Epitope mapping of the alpha-chain of the insulin-like growth factor I receptor using antipeptide antibodies.

    abstract::Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence sim...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1185

    authors: Delafontaine P,Ku L,Ververis JJ,Cohen C,Runge MS,Alexander RW

    更新日期:1994-12-01 00:00:00

  • Skeletal muscle metabolism in experimental heart failure.

    abstract::We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart fail...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0219

    authors: Bernocchi P,Ceconi C,Pedersini P,Pasini E,Curello S,Ferrari R

    更新日期:1996-11-01 00:00:00

  • Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and endothelin 1.

    abstract::The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ e...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0002

    authors: Ballard C,Schaffer S

    更新日期:1996-01-01 00:00:00

  • AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction.

    abstract::We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44(pos)CD45(neg) multipotential mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting collagen that forms a scar and mature into myofibroblasts that express alpha smooth muscle acti...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2013.07.005

    authors: Cieslik KA,Taffet GE,Crawford JR,Trial J,Mejia Osuna P,Entman ML

    更新日期:2013-10-01 00:00:00

  • Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription.

    abstract::Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that extracellular signal-regulated kinase (ERK) 1/2 ac...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2014.06.018

    authors: Huang H,Joseph LC,Gurin MI,Thorp EB,Morrow JP

    更新日期:2014-10-01 00:00:00

  • Dose/response curves of lipoic acid R-and S-forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow.

    abstract::Micromolar concentrations of lipoic acid racemate added to a working rat heart during hypoxia have been previously found to improve aortic flow during subsequent reoxygenation. Since the R-form represents the naturally occurring form of lipoic acid, and the S-form does not reveal a positive influence on ATP synthesis ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(95)90012-8

    authors: Zimmer G,Beikler TK,Schneider M,Ibel J,Tritschler H,Ulrich H

    更新日期:1995-09-01 00:00:00

  • The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size.

    abstract::The two-pore domain potassium (K(+)) channel TWIK-1 (or K2P1.1) contributes to background K(+) conductance in diverse cell types. TWIK-1, encoded by the KCNK1 gene, is present in the human heart with robust expression in the atria, however its physiological significance is unknown. To evaluate the cardiac effects of T...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2016.04.006

    authors: Christensen AH,Chatelain FC,Huttner IG,Olesen MS,Soka M,Feliciangeli S,Horvat C,Santiago CF,Vandenberg JI,Schmitt N,Olesen SP,Lesage F,Fatkin D

    更新日期:2016-08-01 00:00:00

  • Regional biochemical remodeling in non-infarcted tissue of rat heart post-myocardial infarction.

    abstract::Changes in the capacities of ATP-synthesizing reactions were analysed in residual non-infarcted myocardium following myocardial infarction. Rats were subjected to left coronary artery ligation (MI; n = 11) or to sham operation (sham; n = 18). Two months later, hearts were excised, rinsed and buffer-perfused isovolumic...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0143

    authors: Laser A,Ingwall JS,Tian R,Reis I,Hu K,Gaudron P,Ertl G,Neubauer S

    更新日期:1996-07-01 00:00:00

  • Expression of active alpha(1B)-adrenergic receptors in the heart does not alleviate ischemic reperfusion injury.

    abstract::Ischemic preconditioning reduces infarct size and improves cardiac function in various species, including mice. The mechanism for ischemic preconditioning protection is not entirely clear and activation of alpha(1B)-adrenergic receptors (AR) is believed to be involved. Transgenic mice expressing constitutively active ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2000.1201

    authors: Gao XM,Wang BH,Woodcock E,Du XJ

    更新日期:2000-09-01 00:00:00

  • Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts--role of late sodium current and intracellular ion accumulation.

    abstract::The goal of this study was to test the hypothesis that the novel anti-ischemic drug ranolazine, which is known to inhibit late I(Na), could reduce intracellular [Na(+)](i) and diastolic [Ca(2+)](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2008.03.006

    authors: Sossalla S,Wagner S,Rasenack EC,Ruff H,Weber SL,Schöndube FA,Tirilomis T,Tenderich G,Hasenfuss G,Belardinelli L,Maier LS

    更新日期:2008-07-01 00:00:00

  • Extracellular superoxide dismutase regulates cardiac function and fibrosis.

    abstract::Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesiz...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.08.010

    authors: Kliment CR,Suliman HB,Tobolewski JM,Reynolds CM,Day BJ,Zhu X,McTiernan CF,McGaffin KR,Piantadosi CA,Oury TD

    更新日期:2009-11-01 00:00:00

  • New occurrence of atrial natriuretic factor and storage in secretorially active granules in adult rat ventricular cardiomyocytes in long-term culture.

    abstract::Under normal physiological conditions atrial natriuretic factor (ANF) in rat is stored in secretory granules in fetal and adult atrial cardiomyocytes (Cantin et al., 1984; de Bold, 1985), whereas in fetal and neonatal ventricular cardiomyocytes secretory granules are practically absent and ANF is directly secreted via...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1088

    authors: Eppenberger-Eberhardt M,Messerli M,Eppenberger HM,Reinecke M

    更新日期:1993-07-01 00:00:00

  • Cardiac morphogenetic defects and conduction abnormalities in mice homozygously deficient for connexin40 and heterozygously deficient for connexin45.

    abstract::Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity. We found that Cx40/Cx45 double deficiency (Cx40(-/-)/Cx45(+/-)) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth. The majority of Cx40(-/-)/C...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2006.07.005

    authors: Krüger O,Maxeiner S,Kim JS,van Rijen HV,de Bakker JM,Eckardt D,Tiemann K,Lewalter T,Ghanem A,Lüderitz B,Willecke K

    更新日期:2006-11-01 00:00:00

  • Signaling factors in stem cell-mediated repair of infarcted myocardium.

    abstract::Myocardial infarction leads to scar formation and subsequent reduced cardiac performance. The ultimate therapy after myocardial infarction would pursue stem cell-based regeneration. The aim of stem cell-mediated cardiac repair embodies restoration of cardiac function by regeneration of healthy myocardial tissue, which...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2005.05.012

    authors: Vandervelde S,van Luyn MJ,Tio RA,Harmsen MC

    更新日期:2005-08-01 00:00:00

  • Detection of TUNEL-positive cardiomyocytes and c-kit-positive progenitor cells in children with congenital heart disease.

    abstract::The loss of cardiomyocytes by apoptosis and the subsequent replacement by fibrous connective tissues are important features of cardiac remodeling in adult heart disease. In children with CHD, however, the cellular and molecular mechanisms of heart failure have not yet been fully understood because of the anatomical an...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.05.011

    authors: Sato H,Shiraishi I,Takamatsu T,Hamaoka K

    更新日期:2007-09-01 00:00:00

  • Toxic oxygen metabolites and ischemia-reperfusion increase histamine synthesis and release in the isolated rat heart.

    abstract::Histamine is synthetized in the heart, and released by ischemia-reperfusion injury in several species. Histamine has arrhythmogenic, chronotropic, inotropic and vasoactive effects. Cardiac histamine release during ischemia-reperfusion may be mediated by toxic oxygen metabolites. We studied the effect of ischemia-reper...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1005

    authors: Valen G,Kaszaki J,Szabó I,Nagy S,Vaage J

    更新日期:1993-01-01 00:00:00

  • Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway.

    abstract::The insulin receptor substrate (IRS) family plays important roles in cellular growth, signaling, and survival in the brain. We identified IRS6/Dok-5, a member of the IRS family, also expressed in heart. Dok-5 expression level significantly increased during cardiomyocyte differentiation of P19CL6 cells. To understand t...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.09.015

    authors: Wen J,Xia Q,Wang C,Liu W,Chen Y,Gao J,Gong Y,Yin B,Ke Y,Qiang B,Yuan J,Peng X

    更新日期:2009-12-01 00:00:00

  • Quantitation and distribution of beta-tubulin in human cardiac myocytes.

    abstract::Increasing evidence suggests that derangements of cytoskeletal proteins contribute to alterations in intracellular signaling, myocyte function, and the coupling of myocytes to the extracellular matrix during cardiac hypertrophy and failure. Data from animal studies have shown an increased density of beta-tubulin prote...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2002.2105

    authors: Aquila-Pastir LA,DiPaola NR,Matteo RG,Smedira NG,McCarthy PM,Moravec CS

    更新日期:2002-11-01 00:00:00

  • Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins.

    abstract::The aim of this study was to examine whether short- and long-term gene transfer of Ca(2+) handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) (Banding+SER...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.01.003

    authors: Sakata S,Lebeche D,Sakata N,Sakata Y,Chemaly ER,Liang LF,Tsuji T,Takewa Y,del Monte F,Peluso R,Zsebo K,Jeong D,Park WJ,Kawase Y,Hajjar RJ

    更新日期:2007-04-01 00:00:00

  • Microtubules in the heart muscle of the postnatal and adult rat.

    abstract::In the postnatal rat heart, muscle cells continue to divide as well as increase in size. At the same time the cells in the soleus muscle (a slow skeletal muscle) do not divide, although they continue to grow in size. Since microtubules may have a role in orienting intracellular structures in muscle, we determined the ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(85)80087-0

    authors: Cartwright J Jr,Goldstein MA

    更新日期:1985-01-01 00:00:00

  • Aspirin and clopidogrel treatment impair nitric oxide biosynthesis by platelets.

    abstract::Aspirin and clopidogrel are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and beta-adrenoceptor (beta-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects (n=19) were ra...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.yjmcc.2008.05.015

    authors: O'Kane PD,Reebye V,Ji Y,Stratton P,Jackson G,Ferro A

    更新日期:2008-08-01 00:00:00

  • Kir2.x inward rectifier potassium channels are differentially regulated by adrenergic alpha1A receptors.

    abstract::Inhibition of I(K1) currents by adrenergic alpha(1) receptors has been observed in cardiomyocytes and has been linked to arrhythmogenesis in an animal model. Both PKC-dependent and PKC-independent pathways have been implied in this regulation. The underlying molecular mechanisms, however, have not been elucidated to d...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.10.008

    authors: Zitron E,Günth M,Scherer D,Kiesecker C,Kulzer M,Bloehs R,Scholz EP,Thomas D,Weidenhammer C,Kathöfer S,Bauer A,Katus HA,Karle CA

    更新日期:2008-01-01 00:00:00

  • Adenosine receptor blockade enhances isoproterenol-induced increases in cardiac interstitial adenosine.

    abstract::The failure of adenosine receptor antagonists to consistently attenuate metabolic coronary vasodilation suggests that adenosine is not a primary regulator of functional hyperemia. An alternative hypothesis, however, is that metabolic stimulation of the heart in the presence of an adenosine receptor antagonist results ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(91)90132-6

    authors: Heller LJ,Dole WP,Mohrman DE

    更新日期:1991-08-01 00:00:00

  • Gender influences on sarcoplasmic reticulum Ca2+-handling in failing human myocardium.

    abstract::Gender has recently been implicated as an important modulator of cardiovascular disease. However, it is not known how gender may specifically influence the Ca2+-handling deficits that characterize the depressed cardiac contractility of human heart failure. To elucidate the contributory role of gender to sarcoplasmic r...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1394

    authors: Dash R,Frank KF,Carr AN,Moravec CS,Kranias EG

    更新日期:2001-07-01 00:00:00

  • Endothelial dysfunction in adiponectin deficiency and its mechanisms involved.

    abstract::Endothelial dysfunction is the earliest pathologic alteration in diabetic vascular injury and plays a critical role in the development of atherosclerosis. Plasma levels of adiponectin (APN), a novel vasculoprotective adipocytokine, are significantly reduced in diabetic patients, but its relationship with endothelial d...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2008.10.014

    authors: Cao Y,Tao L,Yuan Y,Jiao X,Lau WB,Wang Y,Christopher T,Lopez B,Chan L,Goldstein B,Ma XL

    更新日期:2009-03-01 00:00:00

  • Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction.

    abstract::Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth fact...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2000.1146

    authors: Nakahama M,Murakami T,Kusachi S,Naito I,Takeda K,Ohnishi H,Komatsubara I,Oka T,Ninomiya Y,Tsuji T

    更新日期:2000-06-01 00:00:00

  • The effect of alterations to action potential duration on beta-adrenoceptor-mediated aftercontractions in human and guinea-pig ventricular myocytes.

    abstract::Aftercontractions induced by beta-adrenoceptor stimulation in human and guinea-pig cardiomyocytes may be related to changes in action potential duration (APD). We investigated the effects of altering APD during the occurrence of isoproterenol-induced aftercontractions, using the KATP channel openers cromakalim and lem...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0385

    authors: Tweedie D,O'Gara P,Harding SE,MacLeod KT

    更新日期:1997-05-01 00:00:00

  • Rare non-coding Desmoglein-2 variant contributes to Arrhythmogenic right ventricular cardiomyopathy.

    abstract::Arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to variants in the coding sequence of desmosomal genes. The potential contribution of non-coding desmoglein-2 (DSG2) variants for development of ARVC is undescribed. We sequenced 1450 base pairs upstream of ATG in the DSG2 gene in 65 unrelated pati...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.04.029

    authors: Christensen AH,Andersen CB,Wassilew K,Svendsen JH,Bundgaard H,Brand SM,Schmitz B

    更新日期:2019-06-01 00:00:00

  • Mutation that dramatically alters rat titin isoform expression and cardiomyocyte passive tension.

    abstract::Titin is a very large alternatively spliced protein that performs multiple functions in heart and skeletal muscles. A rat strain is described with an autosomal dominant mutation that alters the isoform expression of titin. While wild type animals go through a developmental program where the 3.0 MDa N2B becomes the maj...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2008.02.272

    authors: Greaser ML,Warren CM,Esbona K,Guo W,Duan Y,Parrish AM,Krzesinski PR,Norman HS,Dunning S,Fitzsimons DP,Moss RL

    更新日期:2008-06-01 00:00:00

  • Cardiomyocyte cell cycling, maturation, and growth by multinucleation in postnatal swine.

    abstract:BACKGROUND:Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative c...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2020.07.004

    authors: Velayutham N,Alfieri CM,Agnew EJ,Riggs KW,Baker RS,Ponny SR,Zafar F,Yutzey KE

    更新日期:2020-09-01 00:00:00