Abstract:
:The BH3-only proteins, including BNip3, are members of the Bcl-2 family of cell death-regulating factors. Whereas proteins such as Bax and Bak play a central role in most forms of apoptosis, the BH3-only proteins appear to modulate apoptosis through cell type- and signal-specific pathways. This review will focus on our studies of the specific role of BNip3 in cardiac myocyte apoptotic signaling during ischemia. We recently showed that hypoxia in the presence of high glucose leads to progressive acidosis of cardiac myocytes in culture. Cardiac myocytes are resistant to chronic hypoxia at neutral pH but undergo extensive death when the [pH]o drops below 6.5. A micro-array analysis of 20,000 genes identified the pro-apoptotic Bcl-2 family member BNip3 as one of the most strongly upregulated of >100 hypoxia-inducible genes in cardiac myocytes. BNip3 mRNA increased by 12-fold, and BNip3 protein by sixfold, during 24 h of hypoxia; BNip3 protein accumulation was further enhanced by acidosis. BNip3 was loosely bound to mitochondria under conditions of neutral hypoxia but became more tightly associated at acid pH, coincident with opening of the mitochondrial permeability transition pore (MPTP). Subsequent DNA fragmentation and cell death were not blocked by caspase inhibitors, but were inhibited by antisense BNip3 oligonucleotides and MPTP inhibitors, indicating that BNip3 activates an atypical programmed death pathway with features of both apoptosis and necrosis. The sequential induction and activation of BNip3 by hypoxia and acidosis provide a molecular basis for the observation that chronic hypoxia at neutral pH does not promote apoptosis or activate caspases in neonatal cardiac myocytes.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Webster KA,Graham RM,Bishopric NHdoi
10.1016/j.yjmcc.2004.11.007keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
35-45issue
1eissn
0022-2828issn
1095-8584pii
S0022-2828(04)00328-1journal_volume
38pub_type
杂志文章,评审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
更新日期:2013-10-01 00:00:00
abstract::The effects of preventing oxidative phosphorylation on pHi were compared in papillary muscles from right ventricles of normal and pressure-overloaded ferret hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days. pHi was recorded with pH-sensitive microelectrodes. Resting pHi and the relationship ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90043-8
更新日期:1995-03-01 00:00:00
abstract::Short duration exposure to cellular stresses have been shown to activate p38 mitogen-activated protein kinase (MAPK) in cultured rat ventricular cardiomyocytes and isolated perfused hearts; however, effects of chronic stress on p38 MAPK are not well understood. This study determined whether alterations in the p38 MAPK...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1415
更新日期:2001-08-01 00:00:00
abstract::Mammalian cardiomyocytes withdraw from the cell cycle shortly after birth, although it remains unclear how cardiomyocyte cell cycles behave during development. Compared to conventional immunohistochemistry in static observation, time-lapse imaging can reveal comprehensive data in hard-to-understand biological phenomen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.03.020
更新日期:2014-07-01 00:00:00
abstract::Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibil...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90260-2
更新日期:1983-10-01 00:00:00
abstract::Disturbances of cellular calcium homeostasis due to oxidative stress are involved in reperfusion associated phenomena like myocardial stunning and reperfusion induced arrhythmias. This study investigates the effect of the major neutrophil-derived oxidant hypochlorous acid (HOCl) on the l-type calcium current (ICa,L) o...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0749
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Fabry disease is an X-linked disease caused by mutations in α-galactosidase A (GLA); these mutations result in the accumulation of its substrates, mainly globotriaosylceramide (Gb3). The accumulation of glycosphingolipids induces pathogenic changes in various organs, including the heart, and Fabry cardiomyop...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.07.246
更新日期:2018-08-01 00:00:00
abstract::Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.07.020
更新日期:2015-10-01 00:00:00
abstract::Loss of T-tubules (TT), sarcolemmal invaginations of cardiomyocytes (CMs), was recently identified as a general heart failure (HF) hallmark. However, whether TT per se or the overall sarcolemma is altered during HF process is still unknown. In this study, we directly examined sarcolemmal surface topography and physica...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.05.006
更新日期:2014-09-01 00:00:00
abstract::Protein kinase C epsilon (PKCε) activation controls fibroblast growth factor-2 (FGF-2) angiogenic signaling. Here, we examined the effect of activating PKCε on FGF-2 dependent vascular growth and endothelial activation. ψεRACK, a selective PKCε agonist induces pro-angiogenic responses in endothelial cells, including f...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.07.006
更新日期:2013-10-01 00:00:00
abstract::It is still a matter of debate, whether decreased protein expression of SERCA 2a and phospholamban (PLB), or alterations in the phosphorylation state of PLB are responsible for the reduced SERCA 2a function in failing human myocardium. Thus, in membrane preparations from patients with terminal heart failure due to idi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0897
更新日期:1999-03-01 00:00:00
abstract::Atrial fibrosis has been strongly associated with the presence of heart diseases/arrhythmias, including congestive heart failure (CHF) and atrial fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the subject of intense recent investigation since it is the most commonly encountered arrhythmi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.09.001
更新日期:2010-03-01 00:00:00
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
更新日期:2016-08-01 00:00:00
abstract::RP58866 (1-[-2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4- (3,4-dimethoxyphenyl)-piperidine), a specific blocker of the inwardly rectifying K+ current (IK1), is an extremely effective antiarrhythmic agent in rat, rabbit and primate (marmoset) isolated hearts in the settings of acute ischaemia and reperfusion (Rees and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1995.0046
更新日期:1995-12-01 00:00:00
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
更新日期:1997-05-01 00:00:00
abstract::This study addresses the role of polyamines and their rate limiting enzyme, ornithine decarboxylase in regulation of macromolecular transport of two macromolecules, fluorescein and horseradish peroxidase, across coronary capillaries. Rat hearts were isolated and retrogradely perfused through the aorta (Langendorff met...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1046
更新日期:1994-03-01 00:00:00
abstract::Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes encoding sarcomere proteins. The mechanisms involved in the development of cardiac hypertrophy and heart failure remain poorly understood. Global proteomic profiling was used to study the cardiac proteome of mice predisposed to develo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.08.015
更新日期:2010-05-01 00:00:00
abstract::The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrh...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2015.02.013
更新日期:2015-05-01 00:00:00
abstract::To examine cardiac myosin gene structure and expression in a non-human primate model for human heart development and disease, we have constructed a cDNA library from baboon atrium and used baboon beta-myosin heavy chain (beta-MHC)* cDNA probes to isolate atrial MHC clones. The nucleotide sequence of one such clone, la...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90805-5
更新日期:1989-10-01 00:00:00
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
更新日期:2015-07-01 00:00:00
abstract::Exposure to carbon monoxide (CO) during the fetal and neonatal period was used to evaluate cardiac ventricular regional weight and myocyte growth response to an increased hemodynamic load. Date-mated Sprague-Dawley rats inhaled 200 ppm CO from day 7 of pregnancy until parturition; another group of pregnant rats inhale...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80913-0
更新日期:1986-05-01 00:00:00
abstract::The ability of the myocardium to successfully adapt to cardiac injury ultimately determines whether the heart will decompensate and fail, or whether instead it will maintain preserved function. Despite the importance of the myocardial response to cardiac injury, very little is known with respect to the biochemical mec...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2004.05.028
更新日期:2004-10-01 00:00:00
abstract::Fibroblasts play a pivotal role in cardiac remodeling and the development of heart failure through the deposition of extra-cellular matrix (ECM) proteins and also by affecting cardiomyocyte growth and function. The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system in health and disease and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.12.003
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Heat shock proteins (hsp) constitute an endogenous stress response that protects cells from injury. Most work on these important proteins has focused on the immediate response to acute stress in cell culture systems and mammalian models of heart disease. Little is known about the expression of the hsps in hu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0646
更新日期:1998-04-01 00:00:00
abstract::We examined the relative roles of the mitogen-activated protein kinases (MAPK) in mediating the alpha1-adrenergic receptor (alpha1-AR) stimulated hypertrophic phenotype in adult rat ventricular myocytes (ARVM). Norepinephrine (NE; 1 microM) in the presence of the beta -AR antagonist propranolol (Pro; 2 microM) caused ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1348
更新日期:2001-04-01 00:00:00
abstract::Ventricular trabeculae from adult and newborn ferret heart were chemically skinned by Triton X-100 which disrupts all cellular membranes. In newborn preparations, maximal Ca(2+)-activated tension was two times smaller than in adult fibres while Ca2+ sensitivity was higher. Caffeine (10 mM) and cyclopiazonic acid (100 ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0119
更新日期:1996-06-01 00:00:00
abstract::Iron overload is associated with long-term cardiac iron accumulation and tissue changes such as fibrosis. To determine short-term iron-dependent changes in expression of genes associated with iron homeostasis and fibrosis we measured mRNA on Northern blots prepared from cultured rat neonatal cardiomyocytes and non-myo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1068
更新日期:2000-02-01 00:00:00
abstract::Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of t...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90090-x
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:A higher expression/activity of type 1 serine/threonine protein phosphatase 1 (PP1) may contribute to dephosphorylation of cardiac regulatory proteins triggering the development of heart failure. OBJECTIVE:Here, we tested the putatively protective effects of PP1 inhibitor-2 (I2) overexpression using a heart ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.10.022
更新日期:2018-12-01 00:00:00
abstract::Nitric oxide, which is produced endogenously within cardiac myocytes by three distinct isoforms of nitric oxide synthase, is a key regulator of myocardial function. This review will focus on the regulation of myocardial function by each nitric oxide synthase isoform during health and disease, with a specific emphasis ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2008.07.015
更新日期:2008-11-01 00:00:00