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 similarity to the insulin receptor (IR), and the putative ligand-specific binding site has been localized to a cysteine-rich region (CRR) of the alpha-chain. To obtain insights into antigenic determinants of the IGF IR, we raised a panel of site-specific polyclonal antibodies against short peptide sequences N-terminal to and within the CRR. Several antibodies raised against linear epitopes within the CRR bound to solubilized and native rat and human IGF IR by ELISA, did not cross-react with IR, but unexpectedly failed to inhibit 125I-IGF I binding. A polyclonal antibody directed against a 48-amino acid synthetic peptide, corresponding to a region of the CRR postulated to be essential for ligand binding, failed to react with either solubilized, reduced or intact IGF IR. Three antibodies specific for the N-terminus of the alpha-chain reacted with solubilized and native IGF IR. One of these, RAB 6, directed against amino acids 38-44 of the IGF IR, inhibited 125I-IGF I binding to rat aortic smooth muscle cells (RASM) and to IGF IR/3T3 cells (overexpressing human IGF IR) by up to 45%. Immunohistochemical analysis revealed strong IGF IR staining in the medial smooth muscle cell layer of rat aorta. These findings are consistent with a model wherein conformational epitopes within the CRR and linear epitopes within the N-terminus of the alpha-chain contribute to the IGF I binding pocket. These antibodies should provide a valuable tool to study structure-function relationships and in vivo regulation of the IGF IR.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Delafontaine P,Ku L,Ververis JJ,Cohen C,Runge MS,Alexander RWdoi
10.1006/jmcc.1994.1185subject
Has Abstractpub_date
1994-12-01 00:00:00pages
1659-73issue
12eissn
0022-2828issn
1095-8584pii
S0022282884711850journal_volume
26pub_type
杂志文章abstract::In essential hypertension it has been hypothesized that there is a generalized derangement in cellular Ca2+ homeostasis. The aim of this study was to assess whether there is functional evidence for increased vulnerability to Ca overload in cardiomyocytes derived from age-matched (11-week) normotensive Wistar-Kyoto (WK...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0067
更新日期:1996-04-01 00:00:00
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
更新日期:1999-05-01 00:00:00
abstract::Quin2 is a fluorescent Ca2+-sensitive indicator which in its acetoxymethyl ester form can be loaded into the cytosolic compartment of cells without any disruption of the plasma membrane. Quin2 has been used with many cell types to measure changes of [Ca2+]i in response to hormones and other stimuli. In this report we ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80919-1
更新日期:1986-05-01 00:00:00
abstract::The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 31...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80433-3
更新日期:1986-12-01 00:00:00
abstract::To understand better the pathophysiological roles of the vagal efferent system in ischemic heart diseases, we examined endogenous acetylcholine (ACh) release in the myocardium in vivo. Acute myocardial ischemia was induced in anesthetized cats by a 60-min occlusion of the left anterior descending coronary artery (LAD)...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1087
更新日期:2000-03-01 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::The transcription factor scleraxis has been implicated in regulating the development of collagen-rich tissues such as tendons and cardiac valves, but its role in general collagen synthesis in the heart is unknown. Scleraxis expression in cardiac fibroblasts was examined, and its ability to regulate gene expression of ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.03.024
更新日期:2009-08-01 00:00:00
abstract::There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxyge...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0850
更新日期:1999-01-01 00:00:00
abstract::The aim of the study was to test if pre-ischemic treatment with bradykinin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion, and if any such protection is dependent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also inv...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0226
更新日期:1996-12-01 00:00:00
abstract::It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.07.001
更新日期:2013-10-01 00:00:00
abstract::Growing evidence suggests that the beta1-adrenoceptor-directed autoimmune mechanism may play an important role in the pathogenesis of idiopathic dilated cardiomyopathy. The aim of this study is to further study the effect of specific immunoabsorption of anti-beta1-adrenoceptor autoantibodies on cardiac structure and f...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.04.016
更新日期:2006-07-01 00:00:00
abstract::Recent improvements in survival from AIDS have been accompanied by an increased recognition of the potential importance of other manifestations of HIV infection, including cardiomyopathy. Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. We previous...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.10.006
更新日期:2006-01-01 00:00:00
abstract::31P-NMR was used to monitor myocardial bioenergetics in compensated and failing SHHF/MCC-fa(cp) (SHF) rat hearts. The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is a relatively new genetic model in which all individuals spontaneously develop congestive heart failure, most during the second year o...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0587
更新日期:1998-02-01 00:00:00
abstract::Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF)...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0772
更新日期:1998-10-01 00:00:00
abstract:AIMS:Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to β-adrenergic receptor (β-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functio...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.05.025
更新日期:2019-08-01 00:00:00
abstract::The biochemical and physiological effects of GS alpha activation are well known; however, little is known about the anatomical localisation of GS alpha in the myocardium. Knowledge of the localisation might yield insights into G protein function in heart. The utility of immunocytochemistry using immunofluorescent meth...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0400
更新日期:1997-06-01 00:00:00
abstract::Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac f...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.008
更新日期:2019-02-01 00:00:00
abstract::Attenuation of excessive rates of myocardial glycolysis limits proton production and Ca(2+) overload during reperfusion and improves recovery of post-ischemic left ventricular (LV) function. In order to elucidate mechanisms underlying glycolytic inhibition by adenosine (ADO), this study tested the hypothesis that the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.03.014
更新日期:2012-06-01 00:00:00
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
更新日期:2015-05-01 00:00:00
abstract::Recent evidence has shown that the cardioprotection afforded by the late phase of ischemic preconditioning (PC) is mediated by upregulation of inducible nitric oxide synthase (iNOS). However, the specific cardiac cell type(s) that express(es) iNOS in response to ischemic PC remains unknown. Thus, mice underwent a sequ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1482
更新日期:2002-01-01 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::There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atri...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0458
更新日期:1997-08-01 00:00:00
abstract::Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and to what extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.07.008
更新日期:2005-10-01 00:00:00
abstract::Cardiac-specific expression of an activated calcineurin protein in the hearts of transgenic (CLN) mice produces a profound hypertrophy that rapidly progresses to heart failure. While calcineurin is regulated by Ca2+, the potential effects of calcineurin on cardiac myocyte Ca2+ handling has not been evaluated. To this ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1296
更新日期:2001-02-01 00:00:00
abstract::MicroRNAs (miRNAs) are small non-coding RNAs that control expression of complementary target mRNAs. A growing number of miRNAs has been implicated in the pathogenesis of cardiac diseases, mostly based not on functional data, but on the observation that they are dysregulated in diseased myocardium. Consequently, our kn...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.07.010
更新日期:2012-01-01 00:00:00
abstract::Myocardium which has been preconditioned by one or several brief episodes of ischemia has much slower energy utilization during a subsequent sustained episode of ischemia. Since preconditioned tissue also is 'stunned', the reduced energy utilization of preconditioned tissue may be due to reduced contractile effort. Th...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90190-w
更新日期:1991-12-01 00:00:00
abstract::Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.09.007
更新日期:2015-11-01 00:00:00
abstract::We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CT...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90975-8
更新日期:1990-01-01 00:00:00
abstract::The processes of excitation-contraction coupling in cardiac myocytes require enormous amounts of energy in the form of ATP, which is produced by oxidative phosphorylation in mitochondria. Due to the constantly varying workloads of the heart, efficient matching of energy supply to demand is a requisite for proper heart...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2012.07.015
更新日期:2013-02-01 00:00:00
abstract::Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of calori...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.07.012
更新日期:2006-10-01 00:00:00