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 focus on the gene programs that are activated during pathogenic processes, but the removal of damaged proteins and organelles has been underappreciated as playing an important role in the pathogenesis of heart disease. Proteotoxicity refers to the adverse effects of damaged or misfolded proteins and even organelles on the cell. At the cellular level, the ultimate outcome of uncontrolled or severe proteotoxicity is cell death; hence, the pathogenic impact of proteotoxicity is maximally manifested in organs with no or very poor regenerative capability such as the brain and the heart. Evidence for increased cardiac proteotoxicity is rapidly mounting for a large subset of congenital and acquired human heart disease. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteotoxicity as a major pathogenic factor in the heart. This dictates rigorous testing for the efficacy of proteotoxic attenuation as a new strategy to treat heart disease. This review article highlights some recent advances in our understanding of how misfolded proteins can injure and are handled in the cell, examining the emerging evidence for targeting proteotoxicity as a new therapeutic strategy for heart disease. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy."

journal_name

J Mol Cell Cardiol

authors

Sandri M,Robbins J

doi

10.1016/j.yjmcc.2013.12.015

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

3-10

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(13)00364-7

journal_volume

71

pub_type

杂志文章,评审
  • [32P]phosphate autoradiography as an indicator of regional myocardial oxygen consumption?

    abstract::The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1035

    authors: Richards SM,Rattigan S,Colquhoun EQ,Clark MG

    更新日期:1993-03-01 00:00:00

  • Acetylcholine attenuated TNF-α-induced intracellular Ca2+ overload by inhibiting the formation of the NCX1-TRPC3-IP3R1 complex in human umbilical vein endothelial cells.

    abstract::The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca2+ signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. Howe...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2017.04.001

    authors: Zhao M,Jia HH,Liu LZ,Bi XY,Xu M,Yu XJ,He X,Zang WJ

    更新日期:2017-06-01 00:00:00

  • Temperature affects human cardiac sarcoplasmic reticulum energy-mediated calcium transport.

    abstract::Hypothermic cardioplegic solutions are currently used to preserve cardiac function during transportation. However, it has been shown that end-diastolic compliance decreases in donor hearts during reperfusion. Excessively cold temperatures may affect membrane-bound enzymes (Ca2+ ATPase and Ca2+ uptake) which are necess...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1129

    authors: Labow RS,Hendry PJ,Meek E,Keon WJ

    更新日期:1993-10-01 00:00:00

  • Effects of hemodynamic variables on myocardial K+ balance during and after shortlasting ischemia.

    abstract::Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during a...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(89)90673-1

    authors: Aksnes G,Ellingsen O,Rutlen DL,Ilebekk A

    更新日期:1989-12-01 00:00:00

  • Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome.

    abstract::Andersen's syndrome (AS) (which is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features), a hereditary disease, and missense mutations of KCNJ2 (which encodes an inward rectifying potassium channel) have been reported recently. We performed clinical and molecular analyses of a patient with ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(03)00046-4

    authors: Hosaka Y,Hanawa H,Washizuka T,Chinushi M,Yamashita F,Yoshida T,Komura S,Watanabe H,Aizawa Y

    更新日期:2003-04-01 00:00:00

  • Genetic variants associated with risk of atrial fibrillation regulate expression of PITX2, CAV1, MYOZ1, C9orf3 and FANCC.

    abstract::Genome-wide association studies (GWAS) have identified genetic variants in a number of chromosomal regions that are associated with atrial fibrillation (AF). The mechanisms underlying these associations are unknown, but are likely to involve effects of the risk haplotypes on expression of neighbouring genes. To invest...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.06.005

    authors: Martin RI,Babaei MS,Choy MK,Owens WA,Chico TJ,Keenan D,Yonan N,Koref MS,Keavney BD

    更新日期:2015-08-01 00:00:00

  • Impaired cell shortening and relengthening with increased pacing frequency are intrinsic to the senescent mouse cardiomyocyte.

    abstract::Increased heart rate enhances cardiac contractility and accelerates relaxation. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be impaired in senescent myocardium. While senescent myocardium is characterized by decreased sarc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2000.1239

    authors: Lim CC,Apstein CS,Colucci WS,Liao R

    更新日期:2000-11-01 00:00:00

  • Potassium channel remodeling in cardiac hypertrophy.

    abstract::Cardiac hypertrophy is an adaptive process against increased work loads; however, hypertrophy also presents substrates for lethal ventricular arrhythmias, resulting in sudden arrhythmic deaths that account for about one third of deaths in cardiac hypertrophy. To maintain physiological cardiac function in the face of i...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2006.07.021

    authors: Furukawa T,Kurokawa J

    更新日期:2006-11-01 00:00:00

  • Control of steady-state intracellular pH in intact perfused ferret hearts.

    abstract::To elucidate the role of bicarbonate-dependent mechanisms and Na+/H+ exchange in maintenance of physiological intracellular pH (pHi) under various steady-state conditions, phosphorus NMR spectra were taken in isovolumically-contracting, perfused ferret hearts. Switching the perfusate from HCO3-/CO2 to HEPES buffer sig...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1099

    authors: Kusuoka H,Marban E,Cingolani HE

    更新日期:1994-07-01 00:00:00

  • Adaptational response in transcription factors during development of myocardial hypertrophy.

    abstract::Cardiac hypertrophy is characterized, among others, by the molecular events which selectively activate the expression of genes for contractile proteins within individual myocardial cells. As such, myosin light chain 2 (MLC-2), which is upregulated in the hypertrophic state in both rat and human, serves as a marker for...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(95)92019-6

    authors: Doud SK,Pan LX,Carleton S,Marmorstein S,Siddiqui MA

    更新日期:1995-10-01 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

  • Paracrine mechanisms of stem cell reparative and regenerative actions in the heart.

    abstract::Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2010.08.005

    authors: Mirotsou M,Jayawardena TM,Schmeckpeper J,Gnecchi M,Dzau VJ

    更新日期:2011-02-01 00:00:00

  • Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes.

    abstract::We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pHi) and Na+ (Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+ probe), BCECF/A...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1997.0495

    authors: Wolska BM,Averyhart-Fullard V,Omachi A,Stojanović MO,Kallen RG,Solaro RJ

    更新日期:1997-10-01 00:00:00

  • Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning.

    abstract::The concept of metabolic protection of the ischemic myocardium is in constant evolution and has recently been supported by clinical studies. Historically, enhanced glucose metabolism and glycolysis were proposed as anti-ischemic cardioprotection. This hypothesis is supported by the sub-cellular linkage between key gly...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1006/jmcc.2002.2066

    authors: Opie LH,Sack MN

    更新日期:2002-09-01 00:00:00

  • Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.

    abstract::The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible mod...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.07.014

    authors: Kreymborg Kg,Uchida S,Gellert P,Schneider A,Boettger T,Voswinckel R,Wietelmann A,Szibor M,Weissmann N,Ghofrani AH,Schermuly R,Schranz D,Seeger W,Braun T

    更新日期:2010-10-01 00:00:00

  • Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites.

    abstract::The direct effect of oxygen metabolites was studied on isolated perfused rat hearts. Superoxide anion (O2-.) and hydrogen peroxide (H2O2) were generated by adding purine (2.3 mM) and purified xanthine oxidase (0.06 U/ml) to Krebs-Henseleit buffer (pH 7.4). Xanthine oxidase was added to the purine-containing perfusate ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(88)90578-0

    authors: Miki S,Ashraf M,Salka S,Sperelakis N

    更新日期:1988-11-01 00:00:00

  • Mitochondrial complex II participates in normoxic and hypoxic regulation of α-keto acids in the murine heart.

    abstract::α-Keto acids (α-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that α-KA concentrations are regulated by complex II (succinate dehydrogenase=SDH), which represents an intersection between the mitochondrial respiratory chain for ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.09.023

    authors: Mühling J,Tiefenbach M,López-Barneo J,Piruat JI,García-Flores P,Pfeil U,Gries B,Mühlfeld C,Weigand MA,Kummer W,Weissmann N,Paddenberg R

    更新日期:2010-12-01 00:00:00

  • Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium.

    abstract::The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pr...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0012

    authors: Vermeulen JT,Tan HL,Rademaker H,Schumacher CA,Loh P,Opthof T,Coronel R,Janse MJ

    更新日期:1996-01-01 00:00:00

  • Fibronectin expression during physiological and pathological cardiac growth.

    abstract::Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix of most tissues that serves as a bridge between cells and the interstitial collagen meshwork and influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/0022-2828(95)90067-5

    authors: Farhadian F,Contard F,Corbier A,Barrieux A,Rappaport L,Samuel JL

    更新日期:1995-04-01 00:00:00

  • Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo.

    abstract::Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of p...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0719

    authors: Nordt TK,Sawa H,Fujii S,Bode C,Sobel BE

    更新日期:1998-08-01 00:00:00

  • Stretch-induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1/2 and p38alpha MAP kinases.

    abstract::The cardiac renin-angiotensin system (RAS) has been implicated in mediating myocyte hypertrophy, remodeling, and fibroblast proliferation in the hemodynamically overloaded heart. However, the intracellular signaling mechanisms responsible for regulation of angiotensinogen (Ao), a substrate of the RAS system, are large...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2008.09.121

    authors: Lal H,Verma SK,Golden HB,Foster DM,Smith M,Dostal DE

    更新日期:2008-12-01 00:00:00

  • Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.

    abstract:BACKGROUND:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are unknown. We used an experimental approach based upon clinical signs of RVF to delineate functional and biological processes associated with RVF. M...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2014.11.024

    authors: Borgdorff MA,Koop AM,Bloks VW,Dickinson MG,Steendijk P,Sillje HH,van Wiechen MP,Berger RM,Bartelds B

    更新日期:2015-02-01 00:00:00

  • Evidence for a sustained effectiveness of sodium-channel activators in failing human myocardium.

    abstract::Elevation of cytosolic sodium is thought to be correlated with an increase in force of contraction due to an activation of sodium-calcium exchange. We investigated the inotropic response mediated by the new sodium-channel activator BDF 9148 (0.01-100 mumol/l) on failing human myocardium. Force of contraction was studi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(91)90170-q

    authors: Schwinger RH,Böhm M,Mittmann C,La Rosée K,Erdmann E

    更新日期:1991-04-01 00:00:00

  • Cardiac stem cells and myocardial disease.

    abstract::Recent data indicate that the heart is a self-renewing organ and contains a pool of progenitor cells (PCs). According to the new paradigm, this resident population of multipotent undifferentiated cells gives rise to myocytes, endothelial cells, smooth muscle cells and fibroblasts. Understanding the function of cardiac...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2008.05.025

    authors: Kajstura J,Urbanek K,Rota M,Bearzi C,Hosoda T,Bolli R,Anversa P,Leri A

    更新日期:2008-10-01 00:00:00

  • Regulation of L-type calcium channels of vascular smooth muscle cells.

    abstract::Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/s0022-2828(08)80009-0

    authors: Xiong Z,Sperelakis N

    更新日期:1995-01-01 00:00:00

  • Nitric oxide-dependent vasodilation maintains blood flow in true hibernating myocardium.

    abstract::Patients with chronic coronary artery disease may exhibit chronically depressed regional myocardial function, which can be reversed by revascularization. This was called hibernating myocardium, since it was thought that myocardial blood flow was also chronically reduced and since animals during true hibernation are th...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(03)00174-3

    authors: Kudej RK,Vatner SF

    更新日期:2003-08-01 00:00:00

  • Interleukin-1α dependent survival of cardiac fibroblasts is associated with StAR/STARD1 expression and improved cardiac remodeling and function after myocardial infarction.

    abstract:AIMS:One unaddressed aspect of healing after myocardial infarction (MI) is how non-myocyte cells that survived the ischemic injury, keep withstanding additional cellular damage by stress forms typically arising during the post-infarction inflammation. Here we aimed to determine if cell survival is conferred by expressi...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2020.10.013

    authors: Razin T,Melamed-Book N,Argaman J,Galin I,Lowy Y,Anuka E,Naftali-Shani N,Kandel-Kfir M,Garfinkel BP,Brielle S,Granot Z,Apte RN,Conway SJ,Molkentin JD,Kamari Y,Leor J,Orly J

    更新日期:2020-10-30 00:00:00

  • Interactions of H2O2, EGTA and patch pipette recording methods in feline ventricular myocytes.

    abstract::Free radical generating systems produce a sequence of changes in the action potentials of isolated cardiac myocytes. Efforts to understand the nature of the alterations in ionic currents have yielded mixed results. The use of patch-pipettes for voltage-clamp experiments and manipulation of pipette solution composition...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1068

    authors: Barrington PL

    更新日期:1994-05-01 00:00:00

  • A crosstalk between chromatin remodeling and histone H3K4 methyltransferase complexes in endothelial cells regulates angiotensin II-induced cardiac hypertrophy.

    abstract::Angiotensin II (Ang II) induces cardiac hypertrophy and fibrosis in part by stimulating endothelin (ET-1) transcription. The involvement of the epigenetic machinery in this process is largely undefined. In the present study, we examined the epigenetic maneuvering underlying cardiac hypertrophy and fibrosis following E...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2015.02.010

    authors: Weng X,Yu L,Liang P,Li L,Dai X,Zhou B,Wu X,Xu H,Fang M,Chen Q,Xu Y

    更新日期:2015-05-01 00:00:00

  • DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission.

    abstract::Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarcti...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2016.04.008

    authors: Shimizu Y,Lambert JP,Nicholson CK,Kim JJ,Wolfson DW,Cho HC,Husain A,Naqvi N,Chin LS,Li L,Calvert JW

    更新日期:2016-08-01 00:00:00