Uncoupling protein 2 impacts endothelial phenotype via p53-mediated control of mitochondrial dynamics.

Abstract:

RATIONALE:Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. OBJECTIVE:To determine how mitochondria impact endothelial cell function. METHODS AND RESULTS:We report here that stimuli for endothelial cell proliferation evoke strong upregulation of mitochondrial uncoupling protein 2 (UCP2). Analysis in silico indicated increased UCP2 expression is common in highly proliferative cell types, including cancer cells. Upregulation of UCP2 was critical for controlling mitochondrial membrane potential (Δψ) and superoxide production. In the absence of UCP2, endothelial growth stimulation provoked mitochondrial network fragmentation and premature senescence via a mechanism involving superoxide-mediated p53 activation. Mitochondrial network fragmentation was both necessary and sufficient for the impact of UCP2 on endothelial cell phenotype. CONCLUSIONS:These data identify a novel mechanism whereby mitochondria preserve normal network integrity and impact cell phenotype via dynamic regulation of UCP2.

journal_name

Circ Res

journal_title

Circulation research

authors

Shimasaki Y,Pan N,Messina LM,Li C,Chen K,Liu L,Cooper MP,Vita JA,Keaney JF Jr

doi

10.1161/CIRCRESAHA.113.301319

subject

Has Abstract

pub_date

2013-09-13 00:00:00

pages

891-901

issue

7

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.113.301319

journal_volume

113

pub_type

杂志文章
  • The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma.

    abstract::The dystrophin glycoprotein complex (DGC) is a specialization of cardiac and skeletal muscle membrane. This large multicomponent complex has both mechanical stabilizing and signaling roles in mediating interactions between the cytoskeleton, membrane, and extracellular matrix. Dystrophin, the protein product of the Duc...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000126574.61061.25

    authors: Lapidos KA,Kakkar R,McNally EM

    更新日期:2004-04-30 00:00:00

  • Redundancy reduction for improved display and analysis of body surface potential maps. II. Temporal compression.

    abstract::This paper describes use of the Karhunen-Loeve expansion to identify and reduce temporal redundancy in electrocardiographic body surface potential maps (192 body surface leads recorded simultaneously at 1 kHz/channel for approximately 600 msec). Temporal data compression of about 20 to 1 was obtained with accurate rep...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.49.1.197

    authors: Evans AK,Lux RL,Burgess MJ,Wyatt RF,Abildskov JA

    更新日期:1981-07-01 00:00:00

  • Cyclosporine- and FK506-induced sympathetic activation correlates with calcineurin-mediated inhibition of T-cell signaling.

    abstract::Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasm...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.3.596

    authors: Lyson T,Ermel LD,Belshaw PJ,Alberg DG,Schreiber SL,Victor RG

    更新日期:1993-09-01 00:00:00

  • Telomeres and cardiovascular disease: does size matter?

    abstract::Telomeres-the specialized DNA-protein structures at the ends of eukaryotic chromosomes-are essential for maintaining genome stability and integrity and for extended proliferative life span in both cultured cells and in the whole organism. Telomerase and additional telomere-associated proteins are necessary for preserv...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000122141.18795.9C

    authors: Serrano AL,Andrés V

    更新日期:2004-03-19 00:00:00

  • MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo.

    abstract:RATIONALE:MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown. OBJECTIVE:The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vas...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.240150

    authors: Torella D,Iaconetti C,Catalucci D,Ellison GM,Leone A,Waring CD,Bochicchio A,Vicinanza C,Aquila I,Curcio A,Condorelli G,Indolfi C

    更新日期:2011-09-30 00:00:00

  • Swimming causes myosin adaptations in the rat cardiac isograft.

    abstract::To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, female Fischer 344 rats were subjected to chronic swimming, infrarenal cardiac transplantation, or both. Swimming resulted in hypertrophy (11-12%) of the in situ hearts in both the unoperated an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.3.780

    authors: Advani SV,Geenen D,Malhotra A,Factor SM,Scheuer J

    更新日期:1990-09-01 00:00:00

  • Alpha 1-adrenergic and muscarinic cholinergic stimulation of phosphoinositide hydrolysis in adult rat cardiomyocytes.

    abstract::Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores we...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.57.4.532

    authors: Brown JH,Buxton IL,Brunton LL

    更新日期:1985-10-01 00:00:00

  • From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease.

    abstract::Genome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.115.306464

    authors: Nurnberg ST,Zhang H,Hand NJ,Bauer RC,Saleheen D,Reilly MP,Rader DJ

    更新日期:2016-02-19 00:00:00

  • Hydroxyl radical mediates the endothelium-dependent relaxation produced by bradykinin in mouse cerebral arterioles.

    abstract::Bradykinin relaxes arterioles on the brain's surface. This response is endothelium-dependent. The data presented here confirm the hypothesis that hydroxyl free radical mediates this response and may be the endothelium-dependent relaxing factor for bradykinin in this microvascular bed. The response to a locally applied...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.4.601

    authors: Rosenblum WI

    更新日期:1987-10-01 00:00:00

  • Preconditioning of isolated rat heart is mediated by protein kinase C.

    abstract::Catecholamines have been implicated in the phenomenon of ischemic preconditioning. We have previously demonstrated that ischemic preconditioning against postischemic mechanical dysfunction in the isolated rat heart is mediated by the alpha 1-adrenergic receptor. The purpose of this study was to delineate the signal tr...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.76.1.73

    authors: Mitchell MB,Meng X,Ao L,Brown JM,Harken AH,Banerjee A

    更新日期:1995-01-01 00:00:00

  • Heparin increases exercise-induced collateral blood flow in rats with femoral artery ligation.

    abstract::The potential for heparin to enhance the training-induced increase in collateral-dependent blood flow to the distal hind-limb muscles was evaluated after bilateral femoral artery ligation in adult male rats (approximately 350 g). Rats received either saline (n = 34) or heparin (n = 36) injections and were kept sedenta...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.76.3.448

    authors: Yang HT,Ogilvie RW,Terjung RL

    更新日期:1995-03-01 00:00:00

  • Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate.

    abstract::We tested the hypothesis that accumulation of H+ or inorganic phosphate (Pi) is responsible for the early contractile failure of hypoxia by measuring maximal Ca2+-activated pressure and 31P nuclear magnetic resonance spectra in Langendorff-perfused ferret hearts at 30 degrees C. Maximal Ca2+-activated pressure was ide...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.59.3.270

    authors: Kusuoka H,Weisfeldt ML,Zweier JL,Jacobus WE,Marban E

    更新日期:1986-09-01 00:00:00

  • Relationship between changes in left ventricular bipolar electrograms and regional myocardial blood flow during acute coronary artery occlusion in the dog.

    abstract::The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrog...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.45.6.764

    authors: Ruffy R,Lovelace DE,Mueller TM,Knoebel SB,Zipes DP

    更新日期:1979-12-01 00:00:00

  • Ventricular pressure-volume curve indices change with end-diastolic pressure.

    abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.6.772

    authors: Glantz SA

    更新日期:1976-12-01 00:00:00

  • Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine.

    abstract::We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial pho...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.6.1458

    authors: Arai AE,Pantely GA,Anselone CG,Bristow J,Bristow JD

    更新日期:1991-12-01 00:00:00

  • Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates.

    abstract::This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Six...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.6.1020

    authors: Lopez JA,Armstrong ML,Harrison DG,Piegors DJ,Heistad DD

    更新日期:1988-12-01 00:00:00

  • Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle.

    abstract::The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fl...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.2.460

    authors: Yan GX,Kléber AG

    更新日期:1992-08-01 00:00:00

  • Pioglitazone-induced reductions in atherosclerosis occur via smooth muscle cell-specific interaction with PPAR{gamma}.

    abstract:RATIONALE:Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs). OBJECTIVE:To determine whether a PPARγ agonist reduces angiotensin II (Ang II)-induced ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.219089

    authors: Subramanian V,Golledge J,Ijaz T,Bruemmer D,Daugherty A

    更新日期:2010-10-15 00:00:00

  • Intra- and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria.

    abstract::Intracellular potassium activity in guinea pig left atria was measured using potassium ion-selective microelectrodes and conventional microelectrodes. The effects of extracellular potassium concentration and acetylcholine on both intracellular potassium activity and the relationship between the resting membrane potent...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.54.1.65

    authors: Baumgarten CM,Singer DH,Fozzard HA

    更新日期:1984-01-01 00:00:00

  • Limitations of the double sucrose gap voltage clamp technique in tension-voltage determinations on frog atrial muscle.

    abstract::The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inwa...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.1.106

    authors: Tarr M,Trank JW

    更新日期:1976-07-01 00:00:00

  • Evidence for Ca(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex.

    abstract::We have used tryptic digestion to determine whether Ca(2+) can regulate cardiac ryanodine receptor (RyR) channel gating from within the lumen of the sarcoplasmic reticulum (SR) or whether Ca(2+) must first flow through the channel and act via cytosolically located binding sites. Cardiac RyRs were incorporated into bil...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.3.201

    authors: Ching LL,Williams AJ,Sitsapesan R

    更新日期:2000-08-04 00:00:00

  • Effects of intracellular angiotensin II in vascular smooth muscle cells.

    abstract::Angiotensin (Ang) II is present inside vascular smooth muscle cells (VSMCs); however, its intracellular functions, if any, are unknown. We tested the hypothesis that intracellular Ang II exerts effects on cytosolic Ca2+ ([Ca2+]i) in VSMCs. Ang II was administered via microinjection. Intracellular Ang II localization w...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.79.4.765

    authors: Haller H,Lindschau C,Erdmann B,Quass P,Luft FC

    更新日期:1996-10-01 00:00:00

  • Stable expression and coupling of cardiac L-type Ca2+ channels with beta 1-adrenoceptors.

    abstract::A number of neurotransmitters modulate cardiac dihydropyridine-sensitive L-type Ca2+ channels through several homologous G protein-coupled receptors. Previous studies that have examined receptor-Ca2+ channel interactions have suffered because of the coexpression of various receptor subtypes in native cells. To study t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.76.3.335

    authors: Yatani A,Wakamori M,Niidome T,Yamamoto S,Tanaka I,Mori Y,Katayama K,Green S

    更新日期:1995-03-01 00:00:00

  • S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction.

    abstract:RATIONALE:Post-myocardial infarction ventricular remodeling is associated with the expression of a variety of factors including S100B that can potentially modulate myocyte apoptosis. OBJECTIVE:This study was undertaken to investigate the expression and function of S100B and its receptor, the receptor for advanced glyc...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.195834

    authors: Tsoporis JN,Izhar S,Leong-Poi H,Desjardins JF,Huttunen HJ,Parker TG

    更新日期:2010-01-08 00:00:00

  • Anchoring proteins as regulators of signaling pathways.

    abstract::Spatial and temporal organization of signal transduction is coordinated through the segregation of signaling enzymes in selected cellular compartments. This highly evolved regulatory mechanism ensures the activation of selected enzymes only in the vicinity of their target proteins. In this context, cAMP-responsive tri...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.111.262899

    authors: Perino A,Ghigo A,Scott JD,Hirsch E

    更新日期:2012-08-03 00:00:00

  • Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB.

    abstract:RATIONALE:Overexpression of muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, induces proteasomal degradation in cardiomyocytes. The role of endogenous MAFbx in regulating cardiac hypertrophy and failure remains unclear. OBJECTIVE:We investigated the role of MAFbx in regulating cardiac hypertrophy and fu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.238717

    authors: Usui S,Maejima Y,Pain J,Hong C,Cho J,Park JY,Zablocki D,Tian B,Glass DJ,Sadoshima J

    更新日期:2011-07-08 00:00:00

  • Binding of charged ferritin to alveolar wall components and charge selectivity of macromolecular transport in permeability pulmonary edema in rats.

    abstract::Rat lungs were inflated and incubated in either anionic or cationic ferritin, and alveolar and capillary basement membranes were examined by electron microscopy. Cationic ferritin bound to heparan sulfate proteoglycans on the external surface of the alveolar basement membrane, whereas cationic ferritin bound to the la...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.55.2.155

    authors: Brody JS,Vaccaro CA,Hill NS,Rounds S

    更新日期:1984-08-01 00:00:00

  • Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.

    abstract::The signaling pathways involved in the long-term metabolic effects of angiotensin II (Ang II) in vascular smooth muscle cells are incompletely understood but include the generation of molecules likely to affect oxidase activity. We examined the ability of Ang II to stimulate superoxide anion formation and investigated...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.6.1141

    authors: Griendling KK,Minieri CA,Ollerenshaw JD,Alexander RW

    更新日期:1994-06-01 00:00:00

  • Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac muscles.

    abstract::To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000080536.06932.E3

    authors: Ogut O,Brozovich FV

    更新日期:2003-07-11 00:00:00

  • Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle.

    abstract::Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.3.585

    authors: Lab MJ,Lee JA

    更新日期:1990-03-01 00:00:00