Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:040116 (histone)
 44,835 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differences in responsiveness of various vascular beds to pressor hormones have been reported. In our study, we have examined the effects of angiotensin II (Ang II) and vasopressin (AVP) on cytosolic free Ca2+ concentration [( Ca2+]c), protein kinase C (PKC) activity, and prostacyclin (PGI2) production in cultured aortic and mesenteric smooth muscle cells obtained from female Wistar rats. [Ca2+]c was determined using the Ca2+ fluorescent probe fura-2. PKC activity was assessed by the measurement of the phosphorylation of histone III-S, in the presence or absence of phospholipids, both in the cytosolic and particulate fractions. PGI2 production was estimated by a specific radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha. Our results demonstrate that basal production of PGI2 was higher in mesenteric than in aortic smooth muscle cells. In mesenteric cells, the [Ca2+]c, PKC activity, and PGI2 responses to AVP were higher than those induced by Ang II. This situation is the opposite of that observed in aortic smooth muscle cells. These results indicate different sensitivities to AVP and Ang II between vascular smooth muscle cells originating from two types of vessels.
J Cardiovasc Pharmacol 1989
PMID:Comparison of the effects of angiotensin II and vasopressin on cytosolic free calcium concentration, protein kinase C activity, and prostacyclin production in cultured rat aortic and mesenteric smooth muscle cells. 247 23

The possible involvement of nuclear proteins in the pathogenesis of a spontaneously occurring model of congestive cardiomyopathy in turkeys was examined. This model is characterised by cardiac hypertrophy and dilatation, reduced cardiac output and depressed contractility. The protein composition of myocardial nuclei was compared in normal (n = 9) and cardiomyopathic (n = 18) turkeys, 70 to 140 days old. Myopathic hearts as a group have a higher histone content (1.75 +/- 0.09 (SD) mg . mg DNA-1 vs 1.65 +/- 0.07 in controls, P less than 0.01) and histone/nonhistone protein (NHP) ratio (1.07 +/- 0.07 vs 0.95 +/- 0.02 in controls, P less than 0.01). The latter was independent of age and correlated well with the degree of cardiac dilatation. The electrophoretic patterns of chromatin proteins was decreased in myopathic hearts. This decrease was primarily accounted for by lower NHP phosphorylation (5.78 +/- 1.38 pmol 32P . mg prot-1 . 15 min-1 vs 8.33 +/- 0.81 in controls, P less than 0.01). DEAE-Sephacel chromatography separated cyclic AMP-dependent and -independent nuclear protein kinases with similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide gel electrophoresis of phosphorylated nucleoproteins revealed differences in the lower molecular species of NHPs between control and myopathic hearts. There was a significant correlation between NHP phosphorylation and degree of cardiac dilatation (r = -0.78) or contractility as reflected by left ventricular systolic time intervals (r = -0.57). These results suggest that development of this model of spontaneous cardiomyopathy is associated with, and may, in part, be secondary to changes in the composition and function of myocardial nucleoproteins.
Cardiovasc Res 1982 Apr
PMID:Nulceoprotein changes in the hearts of cardiomyopathic turkeys. 710 89

The possible involvement of nuclear proteins in the pathogenesis of cardiomyopathy was studied in a spontaneously occurring and a furazolidone-induced model of turkey cardiomyopathy. Both models are characterised by cardiac hypertrophy and dilatation, systemic hypotension and depressed contractility. The protein composition of myocardial nuclei was compared in normal (n = 9) and cardiomyopathic (spontaneous n = 6, furazolidone-induced n = 21) turkeys. Cardiac nuclei from spontaneously myopathic animals had a higher histone content (1.827 +/- 0.058 (mean +/- SD) mg . mg DNA-1 vs 1.688 +/- 0.187 in controls, P less than 0.05) and histone/nonhistone protein ratio (1.122 +/- 0.020 vs 0.882 +/- 0.128 in controls, P less than 0.01). Nuclear protein phosphorylation was lower in spontaneously cardiomyopathic turkeys primarily because of decreased nonhistone protein phosphorylation (5.100 +/- 0.759 pmol 32 P . mg prot-1 .15 min-1 vs 8.456 +/- 0.886 in controls, P less than 0.01). In contrast, furazolidone-induced cardiomyopathy of similar severity to the spontaneously occurring model was not associated with changes in nucleoprotein composition or degree of phosphorylation. These results indicate that development of spontaneous cardiomyopathy in turkeys may be related to the composition and function of nuclear nonhistone proteins. These changes are not secondary to the cardiac hypertrophy/dilatation accompanying the myopathic process.
Cardiovasc Res 1982 May
PMID:Contrasting effects of spontaneous and induced cardiomyopathy on the nucleoproteins of turkey hearts. 710 94

Vascular remodeling is a key feature of many pathologic states, including atherosclerosis, or hypertension. Vascular smooth muscle cells participate in determining the vessel structure by several mechanisms such as cell migration, cell growth, or cell death (necrosis or apoptosis). Here we report that thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ -adenosine triphosphatase (ATPase), is able to induce apoptosis in human vascular smooth muscle cells (HVSMCs). Apoptosis was assessed by three different methods: differential chromatin binding dye staining. cytoplasmic histone-associated DNA fragments detection by enzyme-linked immunosorbent assay (ELISA) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). When HVSMCs were treated for 1 h with thapsigargin (100 nM-10 microM), there was a concentration-dependent increase in both parameters 24 h after the thapsigargin pulse. When a time-course experiment was performed, both parameters were significantly enhanced from 3 to 6 h after the exposure to thapsigargin. We conclude that thapsigargin promotes apoptosis in HVSMCs, providing a useful tool for the study of programmed cell death in human vascular smooth muscle.
J Cardiovasc Pharmacol 2000 Nov
PMID:Thapsigargin induces apoptosis in cultured human aortic smooth muscle cells. 1106 29

The aim of this study was to clarify the mechanism(s) of an inhibitory effect of cerivastatin on cultured rat vascular smooth muscle cell (VSMC) growth. After being starved, cultured VSMCs were stimulated by 5% fetal bovine serum with either various concentrations of cerivastatin or 10-4 M of mevalonate. Cerivastatin dose-dependently decreased the values of [3H]-thymidine incorporation and cell numbers and the level of phosphorylated extracellular signal-regulated protein kinase 1/2. It also suppressed the level of proliferative cell nuclear antigen in a dose-dependent manner. These reductions were abolished by the addition of mevalonate. Similarly, the level of phosphorylated p38 was also decreased by cerivastatin. In contrast, cerivastatin dose-dependently activated the phosphorylation of both c-jun NH2-terminal protein kinase and activating transcription factor-2, and these activations were abolished by the addition of mevalonate. The levels of phosphorylated Akt and p70 S6 kinase as well as those of Bcl-2 were dose-dependently reduced by cerivastatin, and these reductions were abolished by the addition of mevalonate. Cerivastatin could dose-dependently elevate the levels of CPP32/caspase-3 activity and cytoplasmic histone-associated DNA fragments in VSMCs without causing cytotoxicity. These results indicate that cerivastatin suppresses cell survival and activates the apoptotic cellular signaling in VSMCs, suggesting that it could be effective for preventing the progression of restenosis after angioplasty.
J Cardiovasc Pharmacol 2002 Aug
PMID:Mechanisms of inhibitory effects of cerivastatin on rat vascular smooth muscle cell growth. 1213 57

In response to pathologic stresses such as hypertension or myocardial infarction, the heart undergoes a remodeling process that is characterized by myocyte hypertrophy, myocyte death and fibrosis, resulting in impaired cardiac function and heart failure. Cardiac remodeling is associated with derepression of genes that contribute to disease progression. This review focuses on evidence linking members of the Ca(2+)/calmodulin-dependent protein kinase (CaMK) superfamily, specifically CaMKII, protein kinase D (PKD) and microtubule associated kinase (MARK), to stress-induced derepression of pathological cardiac gene expression through their effects on class IIa histone deacetylases (HDACs).
Cardiovasc Res 2007 Mar 01
PMID:Derepression of pathological cardiac genes by members of the CaM kinase superfamily. 1721 38

Tumour cells are characterized by karyotype instability, which is accompanied by specific events in the chromatin structure and epigenetic patterns. Epigenetics involves heritable changes in the physical and biochemical state of chromatin, which have no effect on DNA sequences; therefore, changes in the nuclear radial arrangement of chromosomes can also be considered epigenetic events. Nuclear radial distributions of select genomic regions have been studied in many tumour cells and are not influenced by aberrations in chromosome number. On the other hand, genes involved in translocations take up new positions midway between the original coding sequences. The differentiation of leukaemia cells with clinically used agents is often accompanied by nuclear repositioning of tumour-related genes. However, the nuclear rearrangement is cell-type specific and not always associated with changes in the transcriptional activity. Similarly, cell type-specific chromatin structure is observed in tumour cells treated with select cytostatics and inhibitors of epigenetic processes, which have significant influences on the histone code. Chromatin structure and histone modifications were also affected by gamma radiation in leukaemia, multiple myeloma, and solid tumour cells. Interestingly, gamma radiation induced loci proximity, which has been suggested to increase the probability of exchange aberrations typically associated with tumour progression.
Cardiovasc Hematol Disord Drug Targets 2009 Mar
PMID:Chromatin structure and epigenetics of tumour cells: a review. 1927 77

Pathological hypertrophy is commonly induced by activation of protein kinases phosphorylating class II histone deacetylases (HDACs) and desuppression of transcription factors, such as nuclear factor of activated T cell (NFAT). We hypothesized that nifedipine, an L-type Ca(2+) channel blocker, inhibits Ca(2+) calmodulin-dependent kinase II (CaMKII) and NFAT, thereby inhibiting pathological hypertrophy. Mice were subjected to sham operation or transverse aortic constriction (TAC) for 2 weeks with or without nifedipine (10 mg/kg/day). Nifedipine did not significantly alter blood pressure or the pressure gradient across the TAC. Nifedipine significantly suppressed TAC-induced increases in left ventricular (LV) weight/body weight (BW; 5.09 +/- 0.80 vs. 4.16 +/- 0.29 mg/g, TAC without and with nifedipine, n = 6,6, p < 0.05), myocyte cross-sectional area (1,681 +/- 285 vs. 1,434 +/- 197 arbitrary units, p < 0.05), and expression of fetal-type genes, including atrial natriuretic factor (35. 9 +/- 6.4 vs. 8.6 +/- 3.3 arbitrary units, p < 0.05). TAC-induced increases in lung weight/BW (7.7 +/- 0.9 vs. 5.5 +/- 0.5 mg/g, p < 0.05) and decreases in LV ejection fraction (65.5 +/- 3.1% vs. 75.7 +/- 3.3%, p < 0.05) were attenuated by nifedipine. Nifedipine caused significant inhibition of TAC-induced activation of NFAT-mediated transcription, which was accompanied by suppression of Thr 286 phosphorylation in CaMKII. Nifedipine inhibited activation of CaMKII and NFAT by phenylephrine, accompanied by suppression of Ser 632 phosphorylation and nuclear exit of HDAC4 in cardiac myocytes. These results suggest that a subpressor dose of nifedipine inhibits pathological hypertrophy in the heart by inhibiting activation of CaMKII and NFAT, a signaling mechanism commonly activated in pathological hypertrophy.
J Cardiovasc Transl Res 2010 Aug
PMID:Nifedipine inhibits cardiac hypertrophy and left ventricular dysfunction in response to pressure overload. 2055 81

Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups from lysine residues of histone proteins, a modification that results in epigenetic modulation of gene expression. Although originally shown to be involved in cancer and neurological disease, HDACs are also found to play crucial roles in arteriosclerosis. This review summarizes the effects of HDACs and HDAC inhibitors on proliferation, migration, and apoptosis of endothelial and smooth muscle cells. In addition, an updated discussion of HDACs' recently discovered effects on stem cell differentiation and atherosclerosis is provided. Overall, HDACs appear to be promising therapeutic targets for the treatment of arteriosclerosis and other cardiovascular diseases.
Cardiovasc Res 2011 Jun 01
PMID:Role of histone deacetylases in vascular cell homeostasis and arteriosclerosis. 2123 51

Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases. Increasing evidence suggests that lineage commitment of stem/progenitor cells is tightly regulated by epigenetic mechanisms. These epigenetic control mechanisms include DNA and histone modifications, which modulate the chromatin structure thereby regulating access of transcription factors. Particularly, the modification of histone acetylation and methylation, which is controlled by families of histone acetylases/deacetylases and methyltransferases/demethylases, respectively, controls stem cell maintenance, differentiation, and function. This review article summarizes our current understanding of epigenetic mechanisms regulating the differentiation of cardiovascular cells, specifically endothelial cells and cardiac muscle lineages. In particular, the article will focus on the enzymes which modify histones and are involved in chromatin remodelling.
Cardiovasc Res 2011 Jun 01
PMID:Epigenetic regulation of cardiovascular differentiation. 2137 4


1 2 3 4 5 Next >>