自引率: 3.3%
被引量: 14031
通过率: 暂无数据
审稿周期: 1.43
版面费用: 暂无数据
国人发稿量: 36
投稿须知/期刊简介:
The Journal of Molecular and Cellular Cardiology, the official organ of the International Society for Heart Research, provides a forum for research papers dealing with the molecular biology, physiology, pharmacology, and pathophysiology of the heart and c
期刊描述简介:
The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.
-
150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion injury in rat heart.
Early contractile dysfunction and the later death of cardiomyocytes are two major problems that can follow myocardial infarction or major cardiovascular surgery that demands ischemic arrest of the heart. Here, we found that 24 h of hypoxia and 1 h of reoxygenation induced the expression of the chaperone ORP150 in cultured rat cardiomyocytes. Inhibition of its induction using an adenovirus to express anti-sense ORP150 significantly enhanced the hypoxia-reoxygenation-induced cardiomyocyte death; cell death was reduced by overexpressing ORP150. Decreased levels of ORP150 expression also enhanced caspase-3 and -8 activation, cytochrome-c release, and DNA fragmentation, suggesting that this chaperone regulates apoptotic cell death. In contrast, increasing the expression of ORP150 in the cardiomyocytes had the opposite effect on the expression of these molecules. Moreover, apoptotic cell death initiated by myocardial ischemia-reperfusion (I/R) was significantly inhibited in vivo by transfecting an ORP150 expression plasmid into whole rat heart using the hemagglutinating virus of Japan (HVJ)-liposome method. Interestingly, ORP150 seemed to preserve calcium homeostasis in cardiomyocytes that underwent ischemia-reoxygenation in vitro. Calpain activity in the cardiomyocytes was enhanced by anti-sense ORP150 and suppressed by sense ORP150. Finally, we examined the functional recovery of rat hearts that overexpressed ORP150 or GFP protein and were subjected to I/R; we found that ORP150 preserved early contractile function after transient ischemia. Our results indicated cytoprotective roles for ORP150 in rat heart and suggested a therapeutic role for the protein both in preventing cardiomyocyte death and in preserving contractile function after ischemic damage.
被引量：13 发表：2005
-
Expression and cellular distribution of alpha(v)integrins in beta(1)integrin-deficient embryonic stem cell-derived cardiac cells.
:beta(1)integrin-deficient (beta(1)-/-) ES cells showed increased differentiation of cardiac cells characterized by reduced adhesion and high beating frequency. Whereas in whole embryoid body outgrowths of beta(1)-/- cells maximum levels of alpha(v), beta(3)and beta(5)integrin mRNA were delayed and transiently upregulated, in cardiac clusters isolated from beta(1)-/- cells, only beta(3)integrin mRNA levels were enhanced in comparison to wild-type (wt) cells. To answer the question, whether alpha(v)and beta(3)integrins may compensate, at least partially, the loss of beta(1)integrin function during cardiac differentiation, the distribution of alpha(v)and beta(3)integrins in beta(1)-/- and wt pacemaker-like cardiac cells was analyzed. A different distribution of alpha(v)and beta(3)integrins in beta(1)-/- v wt cardiac cells was found. In wt cardiac cells, beta(1)integrin was localized in specialized subsarcolemmal regions, in particular, at focal contacts and costameres, but alpha(v)integrin was diffusely distributed. In contrast, in beta(1)-/- cardiac cells, alpha(v)integrin was preponderantly localized at cell membranes, focal contacts and costameres. beta(3)integrin displayed a diffuse pattern both in wt and in beta(1)-/- pacemaker-like cells at early differentiation stages, whereas at terminal stages, beta(3)was colocalized with sarcomeres in wt, but not in beta(1)-/- pacemaker-like cells. Quantitative immunofluorescence analysis revealed increased alpha(v)and beta(3)integrin levels in beta(1)-/- pacemaker-like cardiac cells. Our results led us to conclude that altered cellular distribution of alpha(v)integrin and upregulation of beta(3)integrin correlate with growth and survival of beta(1)-/- cardiac pacemaker-like cells at an early developmental state. However, alpha(v)and beta(3)integrins cannot functionally compensate the loss of beta(1)integrin during terminal differentiation of cardiac cells implicating that cardiomyocytes require specific beta(1)integrin functions for cardiac specialization.
被引量：9 发表：2001
-
Inhibitory activity of antibodies against the human atrial 5-HT(4)receptor.
:Antibodies directed against the second extracellular loop of G protein-coupled receptors have been shown to exert "agonist-like" activities. In order to test the hypothesis that this is a general phenomenon, antibodies were raised in rabbits against a synthetic peptide corresponding to the second extracellular loop of the newly sequenced human cardiac 5-HT(4)receptor. The antibodies were affinity-purified and shown to recognize the 5-HT(4)receptor in immunoblots of Chinese hamster ovary (CHO) cells expressing the receptor. The antibodies had no intrinsic effect but could depress the activation of L -type calcium channel induced by serotonin in human atrial cells. This antagonist-like effect was exerted both by intact IgG and by Fab fragments. These results are physiologically important since it has been shown that the 5-HT(4)receptor could be a target for autoantibodies in mothers at risk of giving birth to children with neonatal atrio-ventricular block.
被引量：6 发表：2001
-
L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts.
:Since the recognition of the importance of calcium ions to cardiac contractility, the effects of alterations in calcium homeostasis on cardiac myocyte function have attracted immense attention. However, the possibility that changes in extracellular calcium concentration or the administration of calcium channel blockers may exert significant effects on cardiac fibroblasts has not hitherto been explored. This communication presents evidence, for the first time, that EGTA, calcium-free incubation and L-type calcium channel blockers increase endogenous superoxide production in adult rat cardiac fibroblasts. A combination of ryanodine and EGTA was found to have an even greater effect. The observations indicate that extracellular calcium levels influence endogenous superoxide production in cardiac fibroblasts and support the postulation that myocardial fibroblasts may contribute to the cardiac effects of calcium channel blockers and alterations in extracellular calcium concentration.
被引量：8 发表：2001
-
Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway.
: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 end, we examined L-type Ca2+ currents (I(Ca)) in left ventricular myocytes. CLN myocytes had larger (approximately 80%) cell capacitance and enhanced I(Ca) density (approximately 20%) compared with non-transgenic (NTG) littermates, but no change in the current-voltage relationship, single-channel conductance or protein levels of alpha 1 or beta 2 subunit of L-type Ca2+ channels. Interestingly, the kinetics of I(Ca) inactivation was faster (approximately two-fold) in CLN myocytes compared with NTG myocytes. Ryanodine application slowed the rate of I(Ca) inactivation in both groups and abolished the kinetic difference, suggesting that Ca2+ dependent inactivation is increased in CLN myocytes due to altered SR Ca2+ release. Treatment of CLN mice with Cyclosporine A (CsA), a calcineurin inhibitor, prevented myocyte hypertrophy and changes in I(Ca) activity and inactivation kinetics. However, there was no direct effect of CsA on I(Ca) in either NTG or CLN myocytes, suggesting that endogenous calcineurin activity does not directly regulate Ca2+ channel activity. This interpretation is consistent with the observation that I(Ca) density, inactivation kinetics and regulation by isoproterenol were normal in cardiac-specific transgenic mice expressing calcineurin inhibitory protein domains from either Cain or AKAP79. Taken together these data suggest that chronic activation of calcineurin is associated with myocyte hypertrophy and a secondary enhancement of intracellular Ca2+ handling that is tied to the hypertrophy response itself.
被引量：18 发表：2001
