Molecular and physiological effects of alpha-tropomyosin ablation in the mouse.

Abstract:

:Tropomyosin (TM) is an integral component of the thin filament in muscle fibers and is involved in regulating actin-myosin interactions. TM is encoded by a family of four alternatively spliced genes that display highly conserved nucleotide and amino acid sequences. To assess the functional and developmental significance of alpha-TM, the murine alpha-TM gene was disrupted by homologous recombination. Homozygous alpha-TM null mice are embryonic lethal, dying between 8 and 11.5 days post coitum. Mice that are heterozygous for alpha-TM are viable and reproduce normally. Heterozygous knockout mouse hearts show a 50% reduction in cardiac muscle alpha-TM mRNA, with no compensatory increase in transcript levels by striated muscle beta-TM or TM-30 isoforms. Surprisingly, this reduction in alpha-TM mRNA levels in heterozygous mice is not reflected at the protein level, where normal amounts of striated muscle alpha-TM protein are produced and integrated in the myofibril. Quantification of alpha-TM mRNA bound in polysomal fractions reveals that both wild-type and heterozygous knockout animals have similar levels. These data suggest that a change in steady-state level of alpha-TM mRNA does not affect the relative amount of mRNA translated and amount of protein synthesized. Physiological analyses of myocardial and myofilament function show no differences between heterozygous alpha-TM mice and control mice. The present study suggests that translational regulation plays a major role in the control of TM expression.

journal_name

Circ Res

journal_title

Circulation research

authors

Rethinasamy P,Muthuchamy M,Hewett T,Boivin G,Wolska BM,Evans C,Solaro RJ,Wieczorek DF

doi

10.1161/01.res.82.1.116

subject

Has Abstract

pub_date

1998-01-09 00:00:00

pages

116-23

issue

1

eissn

0009-7330

issn

1524-4571

journal_volume

82

pub_type

杂志文章
  • An angiotensin II type 1 receptor mutant lacking epidermal growth factor receptor transactivation does not induce angiotensin II-mediated cardiac hypertrophy.

    abstract::We have shown previously that tyrosine 319 in a conserved YIPP motif in the C terminus of angiotensin II (Ang II) type 1 receptors (AT(1)Rs) is essential for transactivation of epidermal growth factor receptor (EGFR) in vitro. We hypothesized that the signaling mechanism mediated through the specific amino acid sequen...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000240147.49390.61

    authors: Zhai P,Galeotti J,Liu J,Holle E,Yu X,Wagner T,Sadoshima J

    更新日期:2006-09-01 00:00:00

  • Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.

    abstract:RATIONALE:Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumula...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.193870

    authors: Xu G,Watanabe T,Iso Y,Koba S,Sakai T,Nagashima M,Arita S,Hongo S,Ota H,Kobayashi Y,Miyazaki A,Hirano T

    更新日期:2009-08-28 00:00:00

  • Effects of antibodies to myosin light chain kinase on contractility and myosin phosphorylation in chemically permeabilized smooth muscle.

    abstract::We have used an immunological approach to investigate the role of myosin light chain phosphorylation (MLC-Pi) in the control of contractility in smooth muscle. Our aim was to specifically inhibit myosin light chain kinase (MLCK) in the presence of physiologically activating levels of Ca2+ so that other putative Ca2(+)...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.2.457

    authors: De Lanerolle P,Strauss JD,Felsen R,Doerman GE,Paul RJ

    更新日期:1991-02-01 00:00:00

  • Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro.

    abstract::The regulation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) was studied in freshly isolated adult rat heart preparations. In contrast to the situation in ventricular myocytes cultured from neonatal rat hearts, stimulation of MAPK activity by 1 mumol/L phorbol 12-myristate 13-acetate (PMA) was not c...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.75.5.932

    authors: Lazou A,Bogoyevitch MA,Clerk A,Fuller SJ,Marshall C J,Sugden PH

    更新日期:1994-11-01 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

  • Cytoskeletal mechanics in pressure-overload cardiac hypertrophy.

    abstract::We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the ca...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.80.2.281

    authors: Tagawa H,Wang N,Narishige T,Ingber DE,Zile MR,Cooper G 4th

    更新日期:1997-02-01 00:00:00

  • Selective antagonism of hormone-induced vasoconstriction by synthetic atrial natriuretic factor in the rat microcirculation.

    abstract::Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.1.42

    authors: Proctor KG,Bealer SL

    更新日期:1987-07-01 00:00:00

  • Sensitization of dog and guinea pig heart myofilaments to Ca2+ activation and the inotropic effect of pimobendan: comparison with milrinone.

    abstract::We compared the effects of the newer inotropic drugs, pimobendan (UD-CG 115 BS) and milrinone (Win 47203), on the electrical, mechanical and biochemical activity of intact and detergent-skinned preparations of cardiac muscle. Both of these agents increased contractile force of guinea pig papillary muscle preparations ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.5.911

    authors: Fujino K,Sperelakis N,Solaro RJ

    更新日期:1988-11-01 00:00:00

  • Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties.

    abstract::The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we construct...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.84.11.1318

    authors: Cao JM,Qu Z,Kim YH,Wu TJ,Garfinkel A,Weiss JN,Karagueuzian HS,Chen PS

    更新日期:1999-06-11 00:00:00

  • Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1.

    abstract::Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000102937.50486.1B

    authors: Kelly BD,Hackett SF,Hirota K,Oshima Y,Cai Z,Berg-Dixon S,Rowan A,Yan Z,Campochiaro PA,Semenza GL

    更新日期:2003-11-28 00:00:00

  • Concentration-dependent effects of protein kinase C-activating and -nonactivating phorbol esters on myocardial contractility, coronary resistance, energy metabolism, prostacyclin synthesis, and ultrastructure in isolated rat hearts. Effects of amiloride.

    abstract::An extensive investigation of the cardiac actions of phorbol esters and the potential role of the Na(+)-H+ exchanger in those actions was carried out using isolated rat hearts. Sixty minutes of perfusion with 10(-9) M phorbol 12-myristate 13-acetate (PMA) or 10(-8) M phorbol 12,13-dibutyrate (PDBu) produced marked car...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.4.1114

    authors: Watson JE,Karmazyn M

    更新日期:1991-10-01 00:00:00

  • Dynamic changes in myocardial matrix and relevance to disease: translational perspectives.

    abstract::The cardiac extracellular matrix (ECM) provides the architectural scaffold to support efficient contraction and relaxation of cardiomyocytes. The elegant design of the ECM facilitates optimal force transduction, electric transmission, intercellular communication, and metabolic exchange within the myocardial microenvir...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.302819

    authors: Li AH,Liu PP,Villarreal FJ,Garcia RA

    更新日期:2014-02-28 00:00:00

  • Combined deficiency of dystrophin and beta1 integrin in the cardiac myocyte causes myocardial dysfunction, fibrosis and calcification.

    abstract::The dystrophin-glycoprotein complex is a large complex of membrane-associated proteins linking the cytoskeleton to the extracellular matrix in muscle. Transmembrane heterodimeric (alphabeta) integrins serve also as cellular adhesion molecules and mechanotransducers. In the animal model for Duchenne muscular dystrophy,...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.173153

    authors: Elsherif L,Huang MS,Shai SY,Yang Y,Li RY,Chun J,Mekany MA,Chu AL,Kaufman SJ,Ross RS

    更新日期:2008-05-09 00:00:00

  • Mechanisms of automaticity in subsidiary pacemakers from cat right atrium.

    abstract::Intracellular recordings were made from eustachian ridge of cat right atrium to determine mechanisms responsible for subsidiary pacemaker automaticity. Pacemaker action potentials exhibited two phases of diastolic depolarization: an initial steeper slope (D1) followed by a more gradual slope (D2). Cesium (1 mM) decrea...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.4.648

    authors: Rubenstein DS,Lipsius SL

    更新日期:1989-04-01 00:00:00

  • Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo.

    abstract::Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This o...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000259559.48597.32

    authors: Willis MS,Ike C,Li L,Wang DZ,Glass DJ,Patterson C

    更新日期:2007-03-02 00:00:00

  • Leukotriene B4 mediates shear rate-dependent leukocyte adhesion in mesenteric venules.

    abstract::Previous studies have demonstrated that low shear rates promote leukocyte adherence to microvascular endothelium in postcapillary venules. The objective of this study was to determine whether an accumulation of inflammatory mediators such as platelet activating factor and leukotriene B4 is responsible for shear rate-d...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.4.906

    authors: Bienvenu K,Russell J,Granger DN

    更新日期:1992-10-01 00:00:00

  • Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms via smooth muscle cell necrosis and inflammation.

    abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.304899

    authors: Wang Q,Liu Z,Ren J,Morgan S,Assa C,Liu B

    更新日期:2015-02-13 00:00:00

  • Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro.

    abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.3.318

    authors: Weinberger MH,Aoi W,Henry DP

    更新日期:1975-09-01 00:00:00

  • Deficiency of Natriuretic Peptide Receptor 2 Promotes Bicuspid Aortic Valves, Aortic Valve Disease, Left Ventricular Dysfunction, and Ascending Aortic Dilatations in Mice.

    abstract:RATIONALE:Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.311194

    authors: Blaser MC,Wei K,Adams RLE,Zhou YQ,Caruso LL,Mirzaei Z,Lam AY,Tam RKK,Zhang H,Heximer SP,Henkelman RM,Simmons CA

    更新日期:2018-02-02 00:00:00

  • Cyclin-dependent kinase inhibitor p27Kip1, but not p21WAF1/Cip1, is required for inhibition of hypoxia-induced pulmonary hypertension and remodeling by heparin in mice.

    abstract::Heparin has growth inhibitory effects on pulmonary artery smooth muscle cell (PASMC) in vitro and in vivo. However, the mechanism has not been fully defined. In this study, we investigated the role of cyclin-dependent kinase inhibitors, p21(WAF1/cip1) (p21) and p27Kip1 (p27), in the inhibitory effect of heparin on PAS...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000188211.83193.1a

    authors: Yu L,Quinn DA,Garg HG,Hales CA

    更新日期:2005-10-28 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

  • The constitutive function of native TRPC3 channels modulates vascular cell adhesion molecule-1 expression in coronary endothelial cells through nuclear factor kappaB signaling.

    abstract:RATIONALE:Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent,...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.213314

    authors: Smedlund K,Tano JY,Vazquez G

    更新日期:2010-05-14 00:00:00

  • UT-A urea transporter protein in heart: increased abundance during uremia, hypertension, and heart failure.

    abstract::Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic ra...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1401.093293

    authors: Duchesne R,Klein JD,Velotta JB,Doran JJ,Rouillard P,Roberts BR,McDonough AA,Sands JM

    更新日期:2001-07-20 00:00:00

  • Mechanisms that regulate macrophage burden in atherosclerosis.

    abstract::Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells. A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. Although technological advances are still nee...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.301174

    authors: Randolph GJ

    更新日期:2014-05-23 00:00:00

  • Balloon-induced right ventricular outflow obstruction: a new approach to control of acute interventricular shunting after myocardial infarction in canines and swine.

    abstract::Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right ven...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.40.4.372

    authors: Babb JD,Waldhausen JA,Zelis R

    更新日期:1977-04-01 00:00:00

  • Angiotensin II-nitric oxide interaction on sympathetic outflow in conscious rabbits.

    abstract::Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotens...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.4.496

    authors: Liu JL,Murakami H,Zucker IH

    更新日期:1998-03-09 00:00:00

  • Differences in transient outward currents of feline endocardial and epicardial myocytes.

    abstract::Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.5.1287

    authors: Furukawa T,Myerburg RJ,Furukawa N,Bassett AL,Kimura S

    更新日期:1990-11-01 00:00:00

  • Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival.

    abstract:RATIONALE:Yes-associated protein (YAP), the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEA (transcriptional enhancer activator)-domain sequence-specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.304457

    authors: Lin Z,Zhou P,von Gise A,Gu F,Ma Q,Chen J,Guo H,van Gorp PR,Wang DZ,Pu WT

    更新日期:2015-01-02 00:00:00

  • Expression of a mutant (Arg92Gln) human cardiac troponin T, known to cause hypertrophic cardiomyopathy, impairs adult cardiac myocyte contractility.

    abstract::The mechanism(s) by which mutations in sarcomeric proteins cause hypertrophic cardiomyopathy (HCM) remains unknown. A leading hypothesis proposes that mutant sarcomeric proteins impair cardiac myocyte contractility, providing an impetus for compensatory hypertrophy. To test this hypothesis, we determined the impact of...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.81.1.76

    authors: Marian AJ,Zhao G,Seta Y,Roberts R,Yu QT

    更新日期:1997-07-01 00:00:00

  • Role of Ca2+ in metabolic inhibition-induced norepinephrine release in rat brain synaptosomes.

    abstract::Ischemia and simulated ischemic conditions induce enhanced release of norepinephrine (NE) in the brain and the heart. Although studies with neuronal preparations demonstrated a rise in [Ca2+]i under energy-depleted conditions, such release of NE in the heart appears to be predominantly Ca2+ independent. Since Ca2+ ove...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.80.2.179

    authors: Du XJ,Bobik A,Little PJ,Esler MD,Dart AM

    更新日期:1997-02-01 00:00:00