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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structures of light chains isolated from the human myocardium with idiopathic dilated cardiomyopathy (IDC) were determined and compared with the sequence structures of myosin light chains obtained from control human heart myosin. Sequences were determined by chemical analysis and the identity of N-terminal residues established by mass spectrometry. The N-terminal residues in essential (ELC) and regulatory (RLC) light chains were blocked and were identified to be trimethyl alanine. The amino acid sequences of ELC and RLC from control human myosin revealed a high degree of homology with those purified from rat and chicken cardiac myosin. Comparison with a published partial chemical sequence of the human heart myosin light chains revealed significant variations. However, there was very good agreement with published sequences obtained by molecular biological techniques. Sequences of the light chains from cardiomyopathic myosin revealed no difference in the primary structures when compared with control human heart myosin light chains indicating IDC had no influence on, nor was caused by, altered myosin light chain gene expression.
Mol Cell Biochem 1995 Apr 12
PMID:Human cardiac myosin light chains: sequence comparisons between myosin LC1 and LC2 from normal and idiopathic dilated cardiomyopathic hearts. 765 82

The density and distribution of beta 1- and beta 2-adrenoceptors in the atrioventricular conducting system and interatrial and interventricular septa from human hearts with idiopathic dilated cardiomyopathy and ischemic heart disease was determined by quantitative autoradiography using (-)[125I]cyanopindolol and the selective beta 1-adrenoceptor antagonist CGP 20712A and the selective beta 2-adrenoceptor antagonist ICI 118,551. Both beta 1- and beta 2-adrenoceptors were present in the atrioventricular node, bundle of His, interatrial and interventricular septa. No differences in the density or proportions of beta 1- and beta 2-adrenoceptors in the atrioventricular node, bundle of His, interatrial septum and interventricular septum were observed between hearts with idiopathic dilated cardiomyopathy or ischemic heart disease (P > 0.05) so further analysis did not distinguish between the two aetiologies. The density of beta 1-adrenoceptors was lower in the bundle of His (5.0 +/- 1.7 fmol/mg protein) than in the atrioventricular node (22.2 +/- 5.7 fmol/mg protein, P < 0.05), the interatrial septum (29.6 +/- 4.5 fmol/mg protein, P < 0.001) and interventricular septum (24.9 +/- 5.2 fmol/mg protein, P < 0.005, n = 8 for all values). The atrioventricular node, interatrial and interventricular septa had similar densities of beta 1-adrenoceptors (P = 0.60, ANOVA). The distribution of beta 2-adrenoceptors in the atrioventricular node (21.5 +/- 4.1 fmol/mg protein), bundle of His (12.9 +/- 2.6 fmol/mg protein) and atrial (16.7 +/- 2.3 fmol/mg protein) and septal myocardium (13.8 +/- 2.5 fmol/mg protein, n = 8 for all values) was uniform (P = 0.18, ANOVA). The percentage of beta 1- and beta 2-adrenoceptors in the atrioventricular node, bundle of His, interatrial and interventricular septa was uneven (P < 0.001, ANOVA). There was a higher proportion of beta 2-adrenoceptors in the bundle of His (72 +/- 6%) than in the atrioventricular node (51 +/- 3%, P < 0.01), interatrial septum (36 +/- 1%, P < 0.001) and interventricular septum (36 +/- 1%, P < 0.001).
J Mol Cell Cardiol 1994 Mar
PMID:Autoradiographic localization and quantitation of beta 1- and beta 2-adrenoceptors in the human atrioventricular conducting system: a comparison of patients with idiopathic dilated cardiomyopathy and ischemic heart disease. 791 35

In this study we used 2.5% myocardial homogenates to study sarcoplasmic reticulum (SR) activity of the Ca2+ pump and Ca2+ release channel (CRC) from dogs with congestive heart failure produced by either rapid ventricular pacing or idiopathic dilated cardiomyopathy. We used the fluorescent indicator dye and ratiometric spectrofluorometry to monitor Ca2+ uptake while the CRC was open and closed with ryanodine. We confirmed and extended conclusions derived from previous studies of the same dogs using isolated SR. Compared to controls, activities of dogs with either form of CHF were decreased by 36% for the Ca2+ pump (33.7 +/- 7.3 and 21.6 +/- 4.2 nM/s), 78% for the CRC (10.0 +/- 2.8 and 1.4 +/- 1.2 nM/s), 53% for total Ca2+-cycling (53.1 +/- 8.5 and 24.8 +/- 4.4 nM/s), and 17% for net Ca2+ uptake (23.7 +/- 4.0 and 19.6 +/- 4.0 nM/s). In the absence of SR and mitochondrial activity, ionized Ca2+ concentration in myocardial homogenates were 70% abnormally increased in dogs with CHF, probably due to decreased concentration of Ca2+-binding proteins. Comparison of homogenate and isolated SR activities indicated lower-than-normal membrane yields for dogs with CHF. This fractionation artefact previously resulted in up to 50% overestimation of the degree of downregulation of Ca2+-cycling activities in CHF. The CRC activity was found to be decreased due to decreased activity of the Ca2+-ATPase, decreased CRC content, and inhibition. Decreased CRC energy. Maintenance of net Ca2+-pump activity is expected to maintain the amplitude of the myocardial ionized Ca2+ transient whereas downregulation of the CRC and pump are predicted to reduce the total amount of Ca2+ cycled and slow the rise and fall of the Ca2+ transient.
J Mol Cell Cardiol 1994 Feb
PMID:Compensatory asymmetry in down-regulation and inhibition of the myocardial Ca2+ cycle in congestive heart failure produced in dogs by idiopathic dilated cardiomyopathy and rapid ventricular pacing. 800 78

Calmodulin (CaM) is the primary Ca2+ regulatory protein in cardiac cells, thus alterations in calmodulin would greatly influence the contractile response and may play a role in the abnormal calcium handling observed in human heart failure. We used Northern blot analysis to determine changes in calmodulin mRNA expression in left ventricular tissues isolated from 20 failing and four control human hearts. Only hearts with failure due to idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD) were studied. A human calmodulin cDNA probe 95% homologous to Type 3 CaM was used, which hybridized to a single 2.3 kb mRNA. CaM mRNA levels were expressed as a function of total RNA, as determined by hybridization to an 18S cDNA probe, and as a function of myocyte specific mRNA, as determined by hybridization to a myosin heavy chain (MHC) cDNA probe. In both DCM and IHD, CaM mRNA expression relative to total RNA (CaM/18S), was significantly decreased (45% and 61%, respectively) compared to control hearts. CaM mRNA expression in DCM tissues was also significantly decreased (45%) relative to myocyte specific mRNA (CaM/MHC), when compared to control hearts. In IHD, CaM mRNA was not significantly decreased in relation to myocyte specific mRNA, which suggests a greater loss of myocytes or contractile proteins in IHD as compared with DCM. The decreased expressed of CaM mRNA observed in failing hearts could affect many Ca(2+)-dependent processes, and contribute to the inability of these hearts to handle Ca2+ in a viable manner.
J Mol Cell Cardiol 1994 Jan
PMID:Decreased expression of calmodulin mRNA in human end-stage heart failure. 819 73

During development of the human heart, the atrial isoform of alkali myosin light chain (MLC1A) is expressed in the ventricle. With maturation of the heart, MLC1A expression is completely replaced by that of the adult ventricular myosin light chain, MLC1V. We have evaluated the re-expression of MLC1A as a marker of different disease states of the human ventricle. RNA was isolated from the ventricles of patients with idiopathic dilated cardiomyopathy (CM) and severe congenital cardiac defects (CCD). Northern blot analysis was used to measure the mRNA levels of MLC1A and MLC1V in these samples. As a control, the level of regulatory MLC2V mRNA was also measured. We find that the level of MLC2V mRNA per microgram total ventricular RNA is very similar in CM, CCD and normal human samples. In contrast, we find that MLC1V mRNA levels tend to be reduced in both CM and CCD samples. In the case of the CCD samples, this apparent drop in MLC1V is compensated by expression of the developmental MLC1A isoform. However, in CM patients in end-stage failure, expression of MLC1A is barely detectable. The expression of MLC1A in CCD samples may reflect an adaptive mechanism in response to cardiac overload. The failure to detect substantial MLC1A expression in the CM samples may reflect the failure of such an adaptive mechanism.
J Mol Cell Cardiol 1993 May
PMID:Myosin light chain gene expression associated with disease states of the human heart. 837 17

HLA class II genes (DRB, DQA, DQB, DPA, and DPB) were typed at the DNA level using polymerase chain reaction/sequence-specific oligonucleotide probe analysis in 78 unrelated patients with DCM and 336 unrelated healthy controls to elucidate the HLA alleles or HLA haplotypes associated with DCM. The frequencies of DRB1*1401 (15.4% v 4.5%, RR = 3.90, P < 0.0005, Pc < 0.03), DQB1*0503 (14.1% v 5.4%, RR = 2.93, P < 0.007) and DRB1*1401-DQB1*0503 haplotype (11.5% v 1.5%, RR = 8.24, P < 0.00001, Pc < 0.01) were increased in the DCM patients. The frequency of HLA-DRB1*1101 (9.0% v 3.0%, RR = 3.26, P < 0.02) also was increased in the patients. In addition, the frequencies of DQB1*0604 and DPB1*0401 were increased in the DRB1*1401 and DRB1*1101 negative patients. In contrast, the frequencies of DQB1*0303 (19.2% v 30.7%, RR = 0.55, P < 0.05) and DRB1*0901-DQB1*0303 haplotype (16.7% v 29.8%, RR = 0.49, P < 0.02) were decreased in the DCM group. Disease susceptibility to DCM in the Japanese population, thus, may be controlled in part by a gene (or genes) in close linkage disequilibrium with DRB1*1401-DQB1*0503, DRB1*1101-DQB1*0301, and DQB1*0604-DPB1*0401 haplotypes, while the resistance to DCM may be associated with the DRB1*0901-DQB1*0303 haplotype.
J Mol Cell Cardiol 1995 Oct
PMID:DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy. 857 52

In the normal myocardium matrix metalloproteinases (MMP) are present in the latent form. To examine whether MMP are activated following infarction or idiopathic dilated cardiomyopathy (DCM), we extracted and measured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP activity in infarcted left ventricle (LV), noninfarcted LV and right ventricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Accuracy of the zymographic technique was shown for tissue samples as small as 0.05 mg and was comparable to results obtained by a spectrophotometric method. After normalization for total protein concentration, we found 3 +/- 1% collagenase activity in normal atrial tissue which could be activated to 80-90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV, on the other hand, collagenase activity was 85-95% and 10-20%, respectively, while 5-10% and 3-5%, respectively, in noninfarcted LV. In DCM, collagenolytic activity in the endo and epimyocardium was 75 +/- 5 and 35 +/- 5% in the LV and 35 +/- 7 and 20 +/- 5% in the RV, respectively. Thus, in dilated failing human hearts secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and noninfarcted portions of either ventricle with MI and in both ventricles in DCM. This suggests that an activation of collagenase throughout the myocardium may contribute to its remodeling that includes ventricular dilatation and wall thinning.
Mol Cell Biochem 1996 Feb 09
PMID:Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts. 871 34

This is the first report to determine deoxyribonuclease I (DNase I) levels in the human myocardium and the first to demonstrate an increased DNase I level associated with end-stage heart failure due to idiopathic dilated cardiomyopathy (IDCM) compared to non-diseased heart samples. Left ventricular samples were obtained following transplantation from failing hearts of 13 patients diagnosed with IDCM and from four unused donor hearts. Using a zymogram technique, we show that the DNase I levels of the IDCM heart samples were significantly elevated (range 0.65-2.75 pg DNase I/microgram protein, mean +/- S.E. of 1.69 +/- 0.22 pg/micrograms) compared to four non-diseased, donor heart samples (range 0.12-0.35 pg/microgram protein, mean +/- S.E. of 0.22 +/- 0.05 pg/microgram). The DNase I extracted from heart tissue was characterized by: (1) a co-migration with bovine pancreatic DNase I; (2) a pH dependence consistent with DNase I; (3) a dependence of its activity on both Ca2+ and Mg2+ and an inhibition by Zn2+; and (4) an inhibition of its activity in the presence of monomeric rabbit skeletal muscle actin. The elevated DNase I levels associated with heart failure due to IDCM suggests that apoptosis may be implicated in pathophysiology of this disorder.
J Mol Cell Cardiol 1996 Jan
PMID:Elevated DNase I levels in human idiopathic dilated cardiomyopathy: an indicator of apoptosis? 874 17

Recently, a significant activity of inducible nitric oxide synthase (iNOS) has been reported in biopsies from failing hearts due to idiopathic dilated cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC has been stated. In order to investigate, whether iNOS expression is of pathophysiological relevance in human heart failure, we measured iNOS protein expression and cGMP content in left ventricular myocardium from non-failing and failing human hearts. Immunoblot analysis revealed iNOS protein expression in four out of six failing hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n = 6) or failing hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1). cGMP content was increased by 130% in septic hearts, whereas there was no cGMP increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We conclude, that the induction of iNOS may play a role in contractile dysfunction observed in septic shock, but is unlikely to be of major pathophysiological importance in end-stage heart failure due to IDC, IHD, BMD and TCM.
J Mol Cell Cardiol 1996 Jan
PMID:Expression of inducible nitric oxide synthase in failing and non-failing human heart. 874 24

Abnormalities in intracellular Ca2+ handling play a crucial role in the pathogenesis of heart failure. The reduced capacity of failing human myocardium to restore low resting Ca2+ levels during diastole has been explained by the impairment of Ca2+ uptake into the sarcoplasmic reticulum (SR) via the SR Ca2+ATPase. It is unclear whether Ca2+ATPase function, protein levels, and mRNA steady-state levels correspond to one other, and whether the cause of heart failure, namely idiopathic dilated or ischemic cardiomyopathy, produces different changes. The present study examined SR Ca2+ATPase activity and both mRNA and protein levels of SR Ca2+ATPase, phospholamban, and Gi alpha 2 in left ventricular myocardium from eight nonfailing hearts, from eight hearts of patients with idiopathic dilated cardiomyopathy (DCM), and from six hearts from patients with ischemic cardiomyopathy (ICM). Compared to nonfailing myocardium, the activity of the SR Ca2+ATPase was significantly reduced in failing myocardium from patients with DCM (36%, P < 0.01) and from patients with ICM (37%, P < 0.001). Significantly lower levels of SR Ca2+ATPase mRNA levels (55% and -56%, P < 0.001 for DCM and ICM, respectively) and phospholamban mRNA (45%, P < 0.001 for DCM; 31%, P < 0.05 for ICM) were observed in failing than in nonfailing myocardium. In contrast, no significant changes were observed at the level of proteins, Gi alpha 2 mRNA and protein levels were both significantly increased in failing myocardium. There were no differences between idiopathic dilated and ischemic cardiomyopathy concerning the examined parameter. It is concluded that reduced SR Ca2+ATPase activity contributes to an altered intracellular Ca2+ handling by the SR in both dilated and ischemic cardiomyopathic hearts. However, changes in SR Ca2+ATPase and phospholamban steady-state protein levels do not contribute to these alterations. The dissociation between protein and mRNA levels provides evidence for a posttranscriptional or post-translational regulation of these proteins. The observed alterations are not dependent on the underlying cause of end-stage heart failure.
J Mol Med (Berl) 1996 Jun
PMID:Sarcoplasmic reticulum Ca2+ATPase and phospholamban mRNA and protein levels in end-stage heart failure due to ischemic or dilated cardiomyopathy. 886 13


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