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 reticulum (SR) Ca2+ cycling alterations, the protein levels of SR Ca2+-ATPase (SERCA), phospholamban, and calsequestrin, as well as the site-specific phospholamban phosphorylation status, were quantified in a mixed gender population of failing (n=14) and donor (n=15) myocardia. The apparent affinity (EC50) and the maximal velocity (Vmax) of SR Ca2+-uptake were also determined to lend functional significance to any observed protein alterations. Phospholamban and calsequestrin levels were not altered; however, SERCA protein levels were significantly reduced in failing hearts. Additionally, phospholamban phosphorylation (serine-16 and threonine-17 sites) and myocardial cAMP content were both attenuated. The alterations in SR protein levels were also accompanied by a decreased V(max)and an increased EC50 (diminished apparent affinity) of SR Ca2+-uptake for Ca2+ in failing myocardia. Myocardial protein levels and Ca2+ uptake parameters were then analyzed with respect to gender, which revealed that the decreases in phosphorylated serine-16 were specific to male failing hearts, reflecting increases in the EC50 values of SR Ca2+-uptake for Ca2+, compared to donor males. These findings suggest that although decreased SERCA protein and phospholamban phosphorylation levels contribute to depressed SR Ca2+-uptake and left ventricular function in heart failure, the specific subcellular alterations which underlie these effects may not be uniform with respect to gender.

journal_name

J Mol Cell Cardiol

authors

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

doi

10.1006/jmcc.2001.1394

keywords:

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

1345-53

issue

7

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(01)91394-X

journal_volume

33

pub_type

杂志文章
  • δPKC interaction with the d subunit of F1Fo ATP synthase impairs energetics and exacerbates ischemia/reperfusion injury in isolated rat hearts.

    abstract::Previously, we demonstrated protection against hypoxic injury in neonatal cardiac myocytes and reduced release of cardiac troponin I from perfused rat hearts by a novel peptide inhibitor [NH2-YGRKKRRQRRRMLATRALSLIGKRAISTSVCAGRKLALKTIDWVSFDYKDDDDK-] of the delta protein kinase C (δPKC) interaction with the "d" subunit ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.10.030

    authors: Walker M,Caldwell RW,Yoon Y,Nguyen TT,Johnson JA

    更新日期:2015-12-01 00:00:00

  • Phorbolester inhibits alpha 1-adrenoceptor mediated phosphoinositide breakdown in cardiomyocytes.

    abstract::The regulation of and the intracellular events following alpha 1-adrenergic receptor stimulation of myocardium are not completely understood. The alpha 1-adrenergic stimulation of phosphoinositide breakdown was examined in a culture of neonatal rat ventricular myocytes and the influence of a protein kinase C activator...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(89)90607-x

    authors: Meij JT,Lamers JM

    更新日期:1989-07-01 00:00:00

  • Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced Torsades de Pointes.

    abstract::Various drugs are reported to prolong the QT-interval on the surface ECG, thereby increasing the risk of developing a potentially fatal arrhythmia known as Torsades de Pointes (TdP). TdP case reports for these drugs have often been associated with risk factors such as overdosing, concomitant drugs and/or existing path...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2004.09.001

    authors: Sun Z,Milos PM,Thompson JF,Lloyd DB,Mank-Seymour A,Richmond J,Cordes JS,Zhou J

    更新日期:2004-11-01 00:00:00

  • Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells.

    abstract::Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to inv...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.10.006

    authors: Li X,Weng X,Shi H,Gao R,Wang P,Jia D,Zhang S,Dong Z,Sun X,Yang J,Wang Z,Liu R,Li Y,Qiu Z,Hu K,Sun A,Ge J

    更新日期:2019-12-01 00:00:00

  • Histochemical alterations of acute and chronic doxorubicin cardiotoxicity.

    abstract::Histochemical alterations of acute and chronic doxorubicin (DOX) cardiotoxicity in the mouse were assessed by the localization of succinate dehydrogenase (SDH), coenzyme Q10 (CoQ), cytochrome oxidase (COX), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), reduced glutathione (GSH), and intracellular calcium....

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(83)90330-9

    authors: Aversano RC,Boor PJ

    更新日期:1983-08-01 00:00:00

  • The late Na current as a therapeutic target: where are we?

    abstract::In this article we review the late Na current which functionally can be measured using patch-clamp electrophysiology (INa,late). This current is largely enhanced under pathological myocardial conditions such as ischemia and heart failure. In addition, INa,late can cause systolic and diastolic contractile dysfunction v...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2013.03.001

    authors: Maier LS,Sossalla S

    更新日期:2013-08-01 00:00:00

  • The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations.

    abstract::With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat h...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(92)93172-g

    authors: Walters HL 3rd,Digerness SB,Naftel DC,Waggoner JR 3rd,Blackstone EH,Kirklin JW

    更新日期:1992-10-01 00:00:00

  • Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy.

    abstract::Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.04.019

    authors: Ludke A,Wu J,Nazari M,Hatta K,Shao Z,Li SH,Song H,Ni NC,Weisel RD,Li RK

    更新日期:2015-07-01 00:00:00

  • Calcium modulation of single SR potassium channel currents in heart muscle.

    abstract::The modulating effects of Ca2+ on single K+ channel currents in canine heart sarcoplasmic reticulum were studied using a planar lipid bilayer technique. The open-state probability and the unitary open-state current both decreased gradually as the Ca2+ concentration was reduced from pCa 3 to pCa 7.5. Each single-channe...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1022

    authors: Uehara A,Yasukochi M,Imanaga I

    更新日期:1994-02-01 00:00:00

  • Protection against lipopolysaccharide-induced myocardial dysfunction in mice by cardiac-specific expression of soluble Fas.

    abstract::The mechanisms responsible for myocardial dysfunction in the setting of sepsis remain undefined. Fas ligation with its cognate ligand (FasL) induces apoptosis and activates cellular inflammatory responses associated with tissue injury. We determined whether interruption of Fas/FasL interaction by cardiac-specific expr...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2007.09.016

    authors: Niu J,Azfer A,Kolattukudy PE

    更新日期:2008-01-01 00:00:00

  • The axis of local cardiac endogenous Klotho-TGF-β1-Wnt signaling mediates cardiac fibrosis in human.

    abstract:BACKGROUND:Cardiovascular fibrosis is a major contributor to cardiovascular disease, the primary cause of death in patients with chronic kidney disease (CKD). We previously reported expression of endogenous Klotho in human arteries, and that CKD is a state of Klotho deficiency, resulting in vascular calcification, but ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.09.004

    authors: Liu Q,Zhu LJ,Waaga-Gasser AM,Ding Y,Cao M,Jadhav SJ,Kirollos S,Shekar PS,Padera RF,Chang YC,Xu X,Zeisberg EM,Charytan DM,Hsiao LL

    更新日期:2019-11-01 00:00:00

  • Characterization and expression of a heart-selective alternatively spliced variant of alpha II-spectrin, cardi+, during development in the rat.

    abstract::Spectrin is a large, flexible protein that stabilizes membranes and organizes proteins and lipids into microdomains in intracellular organelles and at the plasma membrane. Alternative splicing occurs in spectrins, but it is not yet clear if these small variations in structure alter spectrin's functions. Three alternat...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.01.001

    authors: Zhang Y,Resneck WG,Lee PC,Randall WR,Bloch RJ,Ursitti JA

    更新日期:2010-06-01 00:00:00

  • Formation of binucleated cardiac myocytes in rat heart: I. Role of actin-myosin contractile ring.

    abstract::Cardiac myocytes in rat hearts lose their ability to undergo cytokinesis between day 3 and day 4, resulting in the formation of binucleated myocytes. Failure in the formation of the actin-myosin contractile ring could cause cardiac myocytes to be defective in cytokinesis. Enzymatically isolated cardiac myocytes from 2...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0381

    authors: Li F,Wang X,Bunger PC,Gerdes AM

    更新日期:1997-06-01 00:00:00

  • Sarcoplasmic reticulum Ca2+ pump blockade decreases O2 use of unloaded contracting rat heart slices: thapsigargin and cyclopiazonic acid.

    abstract::We previously established a new measuring method of the myocardial O2 consumption of mechanically unloaded rat left-ventricular slices. O 2 consumption of unstimulated myocardium corresponds to basal metabolism. We have found O2 consumption of stimulated myocardium to include basal metabolism and O 2 consumption for C...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0630

    authors: Takaki M,Kohzuki H,Kawatani Y,Yoshida A,Ishidate H,Suga H

    更新日期:1998-03-01 00:00:00

  • Myocyte growth and cardiac repair.

    abstract::Introduced several decades ago, the dogma persists that ventricular myocytes are terminally differentiated cells and cardiac repair by myocyte regeneration is completely inhibited shortly after birth. On the basis that cardiac myocytes are unable to divide in the adult heart, myocyte growth under physiologic and patho...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1006/jmcc.2001.1506

    authors: Anversa P,Leri A,Kajstura J,Nadal-Ginard B

    更新日期:2002-02-01 00:00:00

  • Both Na+-K+ ATPase and Na +-H+ exchanger are immediately active upon post-ischemic reperfusion in isolated rat hearts.

    abstract::Limited time resolution has hampered proper evaluation of changes in intracellular Na+ (Na+i) in whole hearts upon post-ischemic reperfusion. In isolated rat hearts perfused at 37 degrees C, we studied the contribution of the Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+i during reperfusion using 23Na NMR a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0597

    authors: Van Emous JG,Schreur JH,Ruigrok TJ,Van Echteld CJ

    更新日期:1998-02-01 00:00:00

  • Effects of alpha1-adrenergic stimulation on L-type Ca2+ current in rat ventricular myocytes.

    abstract::The effect of alpha1-adrenergic stimulation on L-type Ca2+ current (ICa,L) in adult rat ventricular myocytes was investigated using three different methods of current recording. During conventional whole-cell recordings with 5 mm-BAPTA included in the pipette solution, phenylephrine (20 microM) did not increase ICa,L ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0758

    authors: Zhang S,Hiraoka M,Hirano Y

    更新日期:1998-10-01 00:00:00

  • LCZ696 improves cardiac function via alleviating Drp1-mediated mitochondrial dysfunction in mice with doxorubicin-induced dilated cardiomyopathy.

    abstract:AIMS:LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2017.06.003

    authors: Xia Y,Chen Z,Chen A,Fu M,Dong Z,Hu K,Yang X,Zou Y,Sun A,Qian J,Ge J

    更新日期:2017-07-01 00:00:00

  • Appearance and regression of rat pouch tissue.

    abstract::Fibrosis, a consequence of tissue repair, can become a final common pathway to organ failure, if progressive. Prevention and regression of organ fibrosis represent targets of considerable interest. The natural fate of fibrosis differs among various tissues being either persistent, progressive or regressive. Cellular a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1999.0944

    authors: Zhang J,Sun Y,Zhang JQ,Ramires FJ,Weber KT

    更新日期:1999-05-01 00:00:00

  • Structural vs. contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle.

    abstract::Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(88)90597-4

    authors: Jalil JE,Doering CW,Janicki JS,Pick R,Clark WA,Abrahams C,Weber KT

    更新日期:1988-12-01 00:00:00

  • Long-term cell culture of adult mammalian cardiac myocytes: electron microscopic and immunofluorescent analyses of myofibrillar structure.

    abstract::Adult rat heart was dissociated into a single-cell suspension by a retrograde perfusion technique with collagenase and hyaluronidase in Krebs-Ringer phosphate buffer. Long-term culture of these isolated single cardiac muscle cells was established for up to 45 days. Transmission electron microscopy and immunofluorescen...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(83)91342-1

    authors: Nag AC,Cheng M,Fischman DA,Zak R

    更新日期:1983-05-01 00:00:00

  • Proteotoxicity: an underappreciated pathology in cardiac disease.

    abstract::In general, in most organ systems, intracellular protein homeostasis is the sum of many factors, including chromosomal state, protein synthesis, post-translational processing and transport, folding, assembly and disassembly into macromolecular complexes, protein stability and clearance. In the heart, there has been a ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2013.12.015

    authors: Sandri M,Robbins J

    更新日期:2014-06-01 00:00:00

  • Non-coding RNAs as orchestrators of autophagic processes.

    abstract::Autophagy is an important quality control mechanism present in all cells to maintain their cellular homeostasis. An imbalance in the autophagic process had been reported in numerous diseases including cardiovascular disease and is associated with serious consequences. Thus, knowledge of key regulators of cardiac autop...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2015.11.012

    authors: Gupta SK,Thum T

    更新日期:2016-06-01 00:00:00

  • Shear stress-induced activation of Tie2-dependent signaling pathway enhances reendothelialization capacity of early endothelial progenitor cells.

    abstract::Although endothelial progenitor cells (EPCs) play a pivotal role in the endothelial repair following arterial injury and shear stress has a beneficial effect on EPCs, however, the molecular mechanism underlying the influence of EPCs on the endothelial integrity and the regulation of shear stress on the EPC signaling r...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.01.019

    authors: Yang Z,Xia WH,Zhang YY,Xu SY,Liu X,Zhang XY,Yu BB,Qiu YX,Tao J

    更新日期:2012-05-01 00:00:00

  • Myocardial substrate metabolism: implications for diabetic cardiomyopathy.

    abstract::The incidence of mortality from cardiovascular diseases in higher in diabetic patients. The cause of this accelerated cardiovascular disease is multifactorial and, although atherosclerotic cardiovascular disease in association with well-defined risk factors has an influence on morbidity and mortality in diabetics, myo...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/s0022-2828(08)80016-8

    authors: Rodrigues B,Cam MC,McNeill JH

    更新日期:1995-01-01 00:00:00

  • Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass.

    abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin. We recently found that the drug flecainide inhibits RyR2 channels and prevents CPVT in mice and humans. Here we compared the effects of flecainide and tetracaine, a known RyR2 ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.10.005

    authors: Hilliard FA,Steele DS,Laver D,Yang Z,Le Marchand SJ,Chopra N,Piston DW,Huke S,Knollmann BC

    更新日期:2010-02-01 00:00:00

  • Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect.

    abstract:BACKGROUND:Dilated cardiomyopathy (DCM) could be caused by mutations in more than 40 different genes. However, the pathogenic impact of specific mutations is in most cases unknown complicating the genetic counseling of affected families. Therefore, functional studies could contribute to distinguish pathogenic mutations...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.12.015

    authors: Brodehl A,Dieding M,Biere N,Unger A,Klauke B,Walhorn V,Gummert J,Schulz U,Linke WA,Gerull B,Vorgert M,Anselmetti D,Milting H

    更新日期:2016-02-01 00:00:00

  • Soluble epoxide hydrolase activation by S-nitrosation contributes to cardiac ischemia-reperfusion injury.

    abstract::Cardiac ischemia-reperfusion (I/R) injury always accompanies recanalization treatment for myocardial infarction. Here we found soluble epoxide hydrolase (sEH), which metabolizes cardioprotective epoxyeicosatrienoic acids into less effective diols, was rapidly activated during myocardial reperfusion in both mouse and r...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2017.07.006

    authors: Ding Y,Li Y,Zhang X,He J,Lu D,Fang X,Wang Y,Wang J,Zhang Y,Qiao X,Gan LM,Chen C,Zhu Y

    更新日期:2017-09-01 00:00:00

  • A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins.

    abstract::Pacemaker (HCN) channels have a key role in the generation and modulation of spontaneous activity of sinoatrial node myocytes. Previous work has shown that compartmentation of HCN4 pacemaker channels within caveolae regulates important functions, but the molecular mechanism responsible is still unknown. HCN channels h...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.05.013

    authors: Barbuti A,Scavone A,Mazzocchi N,Terragni B,Baruscotti M,Difrancesco D

    更新日期:2012-08-01 00:00:00

  • Lessons from the heart: mirroring electrophysiological characteristics during cardiac development to in vitro differentiation of stem cell derived cardiomyocytes.

    abstract::The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2013.12.011

    authors: van den Heuvel NH,van Veen TA,Lim B,Jonsson MK

    更新日期:2014-02-01 00:00:00