Abstract:
:To determine the regulatory role of prolyl hydroxylation in intracellular cardiac procollagen turnover, we examined the effects of prolyl 4-hydroxylase inhibitors (alpha, alpha-dipyridil, 3,4-dihydroxybenzoic acid ethyl ester, pyridine 2,4-dicarboxylic acid ethyl ester) and ascorbic acid on procollagen metabolism by cultured, neonatal rat cardiac fibroblasts. Ascorbate-deficient fibroblasts showed decreased rates of prolyl hydroxylation and total collagen accumulation without a significant reduction in alpha 1(I) and alpha 1(III) mRNA levels. The fraction of newly synthesized procollagens degraded intracellularly was also substantially increased in ascorbate-deficient cells (50 +/- 7 v 30 +/- 3% in ascorbate-deficient v control fibroblasts; P < 0.05). These findings were associated with increased intracellular accumulation of Type I procollagen, enhanced secretion of "underhydroxylated" pro alpha 1 (I) polypeptide into the cell culture medium, and decreased extracellular Type I collagen deposition. Similar results were obtained by treating cells with alpha, alpha-dipyridil (300 microns), and 3,4-dihydroxybenzoic acid ethyl ester (400 microM) in the presence of ascorbate. A major portion of the enhanced degradation of newly synthesized procollagens occurred within acidic intracellular compartments as indicated by the inhibition of procollagen degradation by chloroquine (25 microM). Inhibition of procollagen secretion by colchicine (0.5 micrograms/ml) enhanced the diversion to, and subsequent intracellular degradation of underhydroxylated procollagens in cardiac fibroblast lysosomes. We conclude that inactivation of prolyl 4-hydroxylase increases intracellular accumulation and intralysosomal degradation of newly synthesized cardiac procollagen polypeptides. These observations suggest that procollagen prolyl hydroxylation may be important in the regulation of collagen accumulation by cardiac interstitial cells during fibrotic processes in vivo
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Eleftheriades EG,Ferguson AG,Spragia ML,Samarel AMdoi
10.1016/s0022-2828(95)90095-0subject
Has Abstractpub_date
1995-08-01 00:00:00pages
1459-73issue
8eissn
0022-2828issn
1095-8584journal_volume
27pub_type
杂志文章abstract::Calcium (Ca(2+)) signaling plays a major role in a wide range of physiological functions including control and regulation of cardiac and skeletal muscle performance and vascular tone. As all Ca(2+) signals require proteins to relay intracellular Ca(2+) oscillations downstream to different signaling networks, a specifi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.06.003
更新日期:2009-10-01 00:00:00
abstract::Cell-based therapy after myocardial infarction (MI) is a promising therapeutic option but the relevant cell subsets and dosage requirements are poorly defined. We hypothesized that cell therapy for myocardial infarction is improved by ex vivo expansion and high-dose transplantation of defined hematopoietic progenitor ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.06.010
更新日期:2008-09-01 00:00:00
abstract::Although the myocardium is capable of utilizing both glucose and fatty acid substrates, glucose metabolism is inhibited in the presence of fatty acid during normal perfusion conditions. Fatty acid regulation of glucose utilization in intact beating rat hearts was studied with 13C-enriched substrates and 13C and 31P NM...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90787-6
更新日期:1989-05-01 00:00:00
abstract::We investigated the role of neuropeptide Y (NPY), abundant in the myocardial sympathetic nervous system and endothelial cells, in angiogenesis during chronic myocardial ischemia. Adult male Yorkshire swine underwent ameroid constrictor placement on the proximal left circumflex coronary artery. After 3 weeks, an osmoti...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.08.022
更新日期:2010-12-01 00:00:00
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
更新日期:2011-02-01 00:00:00
abstract::Mitochondria are the major source of cellular energy (ATP), as well as critical mediators of widespread functions such as cellular redox balance, apoptosis, and metabolic flux. The organelles play an especially important role in the maintenance of cardiac homeostasis; their inability to generate ATP following impairme...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.03.011
更新日期:2020-05-01 00:00:00
abstract::Targeted expression of the SV40 large T-antigen oncoprotein (T-Ag) induces cardiomyocyte proliferation in the atria and ventricles of transgenic mice. Previous studies have identified the p53 tumor suppressor, p107 (a homologue of the retinoblastoma tumor suppressor), and p193 (a novel BH3 only proapoptosis protein) a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1403
更新日期:2001-08-01 00:00:00
abstract::The specific activity of cardiac cathepsin B is significantly decreased by starvation and corticosteroid treatment in vivo, and by exposure of the heart in vitro to insulin, hydrocortisone and cycloheximide. Increases in cathepsin B activity occur following isoproterenol-induced cardiac damage in vivo and exposure in ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90324-3
更新日期:1983-08-01 00:00:00
abstract::The mechanism of the antiadrenergic action of adenosine in the heart was investigated by examining the effects of phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, on beta-adrenergic receptor and non-receptor elicited increases in adenylyl cyclase activity of guinea-pig ventricular membranes. These mem...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90981-7
更新日期:1990-12-01 00:00:00
abstract::Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence sim...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1185
更新日期:1994-12-01 00:00:00
abstract::Increasing bodies of evidence indicate that reactive oxygen species (ROS) produced by mitochondria and other sources play an essential role in mediating ventricular remodeling after myocardial infarction and the development of heart failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment of cel...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2006.08.006
更新日期:2006-11-01 00:00:00
abstract::Cardiac β-adrenergic receptors (β-AR) and Ca2+-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca2+ signaling. Elevated diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activati...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.04.005
更新日期:2017-07-01 00:00:00
abstract::Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1476
更新日期:2001-12-01 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::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
更新日期:2014-02-01 00:00:00
abstract::Beta-adrenergic receptor kinase 1 (beta ARK1) participates in the desensitization of beta-adrenergic receptors by uncoupling the signal transduction. The present study was designed to examine whether neurohumoral increase is crucial for the activation of beta ARK1 in heart failure. Four weeks after the ligation of rat...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.0958
更新日期:1999-06-01 00:00:00
abstract::Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2008.03.007
更新日期:2008-06-01 00:00:00
abstract::We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. Aft...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0711
更新日期:1998-07-01 00:00:00
abstract::The myosin heavy chain (MHC) isoforms, alpha- and beta-MHC, are expressed in developmental- and chamber-specific patterns. Healthy human ventricle contains approximately 2-10% alpha-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of alpha-MHC in failing myocardium is consi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.013
更新日期:2010-05-01 00:00:00
abstract::Myocardial ischemia is associated with accumulation of lyso-phospholipids, including lyso-platelet activating factor, the degradation product and precursor of platelet activating factor. These compounds produce cellular and microvascular damage and, in the myocardium, depression of contractility and arrhythmia. The po...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)91048-a
更新日期:1992-06-01 00:00:00
abstract::Peroxynitrite is a potent oxidant and nitrating species proposed as a direct effector of myocardial damage in a wide range of cardiac diseases. Whether peroxynitrite also acts indirectly, by modulating cell signal transduction pathways in the myocardium, has not been investigated. Here, we examined the ability of pero...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.02.020
更新日期:2005-05-01 00:00:00
abstract::The sulfur-containing beta-amino acid, taurine, is the most abundant free amino acid in cardiac and skeletal muscle. Although its physiological function has not been established, it is thought to play an important role in ion movement, calcium handling, osmoregulation and cytoprotection. To begin examining the physiol...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.001
更新日期:2008-05-01 00:00:00
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
更新日期:2006-11-01 00:00:00
abstract::The possible ischemia-selective Class III anti-arrhythmic action (selective action potential widening in ischemia) of the IKATP blocker glibenclamide was assessed in anesthetized rabbits during ischemia induced by complete occlusion of a coronary artery. Coronary artery occlusion caused an initial prolongation in mono...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0664
更新日期:1998-05-01 00:00:00
abstract::It is increasingly evident that redox-dependent modifications in cellular proteins and signaling pathways (or redox signaling) play important roles in many aspects of cardiac hypertrophy. Indeed, these redox modifications may be intricately linked with the process of hypertrophy wherein there is not only a significant...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2014.02.002
更新日期:2014-08-01 00:00:00
abstract::Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnor...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.04.014
更新日期:2012-08-01 00:00:00
abstract::Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably myocardial infarction and stroke. While reperfusion of ischemic tissue is essential for survival, it also initiates cell death through generation of mitochondrial reactive oxygen ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.08.010
更新日期:2018-10-01 00:00:00
abstract::The metabolism of pantothenic acid (Pa) by cardiac muscle was studied in normal and diabetic rats. Tissue levels of Coenzyme A (CoA) are elevated in the heart during early (6 to 12 h) diabetes, remains at a high level for several days, and then returns to normal or below normal levels. The increase in total tissue CoA...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90605-6
更新日期:1989-07-01 00:00:00
abstract::Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.01.008
更新日期:2008-04-01 00:00:00
abstract::Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.04.018
更新日期:2015-07-01 00:00:00