Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The atrial and ventricular surfaces of the mitral valve are lined by endothelial cells termed endocardial cells, while the valve stroma contains interstitial cells. Bovine mitral valve organ cultures were immunoperoxidase-stained for Factor VIII RAg, alpha smooth muscle actin, and PCNA/cyclin in order to identify the cell types involved in mitral valve wound repair. Factor VIII RAg is a well-characterized endothelial cell marker, alpha smooth muscle actin is an indicator of smooth muscle differentiation and PCNA/cyclin is a marker for S phase. Bovine mitral valve endocardium was Factor VIII RAg positive and remained positive after culturing for 6 days (n = 7). Mitral valve interstitial cells were Factor VIII RAg negative and positive for alpha smooth muscle actin. By 6 days in culture, the lateral edges of the preparations, where the tissue was originally dissected from the mitral valve leaflet, were covered by multiple layers of cells. These cells were Factor VIII RAg negative (n = 7), and hence not endocardial, but were alpha smooth muscle actin positive like interstitial cells. Interstitial cells subjacent to the lateral edges were negative for PCNA/cyclin in uncultured preparations (n = 5), but positive in 12 out of 15 specimens cultured for 6 days. The results suggest that mitral valve interstitial cells are responsible for the repair process seen in the lateral edges of mitral valve organ cultures.
J Mol Cell Cardiol 1992 Jan
PMID:Bovine mitral valve organ culture: role of interstitial cells in repair of valvular injury. 153 92

Recombinant phages that carry the human smooth muscle (enteric type) gamma-actin gene were isolated from human genomic DNA libraries. The amino acid sequence deduced from the nucleotide sequence matches those of cDNAs but differs from the protein sequence previously reported at one amino acid position, codon 359. The gene containing one 5' untranslated exon and eight coding exons extends for 27 kb on human chromosome 2. The intron between codons 84 and 85 (site 3) is unique to the two smooth muscle actin genes. In the 5' flanking region, there are several CArG boxes and E boxes, which are regulatory elements in some muscle-specific genes. Hybridization with the 3' untranslated region, which is specific for the human smooth muscle gamma-actin gene, suggests the single gene in the human genome and specific expressions in enteric and aortic tissues. From characterized molecular structures of the six human actin isoform genes, we propose a hypothesis of evolutionary pathway of the actin gene family. A presumed ancestral actin gene had introns at least sites 1, 2, and 4 through 8. Cytoplasmic actin genes may have directly evolved from it through loss of introns at sites 5 and 6. However, through duplication of the ancestral actin gene with substitutions of many amino acids, a prototype of muscle actin genes had been created. Subsequently, striated muscle actin and smooth muscle actin genes may have evolved from this prototype by loss of an intron at site 4 and acquisition of a new intron at site 3, respectively.
Mol Cell Biol 1991 Jun
PMID:Structure, chromosome location, and expression of the human smooth muscle (enteric type) gamma-actin gene: evolution of six human actin genes. 171 27

Effects of catecholamines on DNA synthesis in vascular smooth muscle cells (VSMC) were investigated in a chemically defined medium that included insulin, transferrin, and sodium selenite. Smooth muscle-rich preparation was obtained from rat aortic media and VSMC were further purified by cell cloning. A clone that was positive for smooth muscle actin and was negative for the coagulation factor VIII was used in this study. The fetal calf serum-induced proliferation was enhanced by alpha-adrenergic and inhibited by beta-adrenergic stimulation. When cells of low passages were used, dose-response curves for norepinephrine were biphasic; when cells were subconfluent, norepinephrine stimulated DNA synthesis at as low as 1 nM and was apparently ineffective at more than 100 nM. When cells were confluent, the effect of norepinephrine was inhibitory at lower concentrations (less than 1 nM) and stimulatory at relatively higher concentrations. Cells of higher passages exhibited only inhibitory effects of the amine. Stimulatory and inhibitory effects on DNA synthesis were mediated through alpha 1- and beta 2-adrenergic receptors, respectively. Thus, the alpha 1-agonist phenylephrine was more potent than the alpha 2-agonist clonidine in stimulating DNA synthesis. An alpha 1-adrenergic antagonist, prazosin, was more effective than the alpha 2-adrenergic antagonist yohimbine in antagonizing the stimulatory effect of norepinephrine. beta-Adrenergic agonists inhibited DNA synthesis with IC50 values in the nanomolar range; the rank order of potency of agonists was isoproterenol greater than salbutamol greater than or equal to (-)-epinephrine much greater than (-)-norepinephrine, consistent with beta 2-receptor specificity. (+)-Epinephrine or (+)-norepinephrine, the stereoisomers of the catecholamines, were ineffective. The inhibitory effects of norepinephrine were reversed by beta-adrenergic antagonists, with the rank order of potency of pindolol greater than butoxamine greater than atenolol, consistent with beta 2-receptor specificity. The dose-response curves of norepinephrine, therefore, seemed to be determined by a balance between alpha 1-receptor-mediated stimulation and beta 2-receptor-mediated inhibition of DNA synthesis. Minimum time required for exhibiting alpha 1-adrenergic or beta 2-adrenergic effects was between 6 and 15 hr, suggesting that the G0 or G1 phase of the cell cycle might be the site of action. These results show that catecholamines dually modulate DNA synthesis in VSMC through specific adrenergic receptors.
Mol Pharmacol 1990 Jan
PMID:Alpha 1-adrenergic stimulation and beta 2-adrenergic inhibition of DNA synthesis in vascular smooth muscle cells. 215 7

The hormone-responsive R3230AC mammary carcinoma, serially transplantable in Fisher rats, shows striking functional and morphological similarities to the normal mammary gland. We have studied its cellular composition by both light and electron microscopy, employing markers of myoepithelial and epithelial cells. We identified two cell types: the major cellular component corresponded to epithelial milk-protein secreting cells, while a second component showed immunocytochemical and ultrastructural characteristics of the myoepithelial cells. These cells were positive with a monoclonal antibody detecting alpha smooth muscle actin. The dual differentiation which normally occurs in breast ducts is therefore reproduced in a malignant experimental tumor. The coexistence of neoplastic cell populations, divergent in morphology and function, that persist in a tumor despite many transplant generations, leads to reconsideration of the relationship between cellular differentiation and malignant transformation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Dual secretory and myoepithelial differentiation in the transplantable R3230AC rat mammary carcinoma. 289 32

We have isolated and characterized two cDNA clones from whole rat stomach, pRV alpha A-19 and pRE gamma A-11, which are specific for the alpha-vascular and gamma-enteric smooth muscle isoactins, respectively. The rat gamma-enteric smooth muscle actin contains a single amino acid substitution of a proline for a glutamine at position 359 of the mature peptide when compared with the chicken gizzard gamma-actin sequence (J. Vandekerckhove and K. Weber, FEBS Lett. 102:219, 1979). Sequence comparisons of the 5' and 3' untranslated (UT) regions of the two smooth muscle actin cDNAs demonstrate that these regions contain no apparent sequence similarities. Additional comparisons of the 5' UT regions of the two smooth muscle actin cDNAs to all other known actin sequences reveal no apparent sequence similarities for the rat gamma-enteric isoactin within the 15 base pairs of sequence currently available, while the rat alpha-vascular isoactin contains two separate sequences which are similar to sequences within the 5' UT regions of the human and chicken alpha-vascular actin genes. A similar comparison of the 3' UT regions of the two smooth muscle actins demonstrates that the alpha-vascular isoactins do not contain the high degree of cross-species sequence conservation observed for the other isoactins and that the gamma-enteric isoactin contains an inverted sequence of 52 nucleotides which is similar to a sequence found within the 3' UT regions of the human, chicken, and rat beta-cytoplasmic isoactins. These observations complicate the apparent cross-species conservation of isotype specificity of these domains previously observed for the other actin isoforms. Northern blot analysis of day 15 rat embryos and newborn, day 19 postbirth, and adult rats demonstrates that the day 15 rat embryo displays low to undetectable levels of smooth muscle isoactin mRNA expression. By birth, the stomach and small intestine show dramatic increases in alpha-vascular and gamma-enteric actin expression. These initially high levels of expression decrease through day 19 to adulthood. In the adult rat, the uterus and aorta differ in their content of smooth muscle isoactin mRNA. These results demonstrate that the gamma-enteric and alpha-vascular isoactin mRNAs are coexpressed to various degrees in tissues which contain smooth muscle.
Mol Cell Biol 1988 Dec
PMID:The development expression of the rat alpha-vascular and gamma-enteric smooth muscle isoactins: isolation and characterization of a rat gamma-enteric actin cDNA. 324 53

A recombinant phage containing an actin gene (lambda Ha201) was isolated from a human DNA library and the structure of the actin gene was determined. The amino acid sequences deduced from the nucleotide sequences of lambda Ha201 were compared with those of six actin isoforms; they matched those of bovine aortic smooth muscle actin, except for codon 309, which was valine (GTC) in lambda Ha201 and alanine (GCN) in bovine aortic smooth muscle actin. Southern blot hybridization experiments showed that the gene of normal human cells did not have the TaqI-sensitive site around position 309, whereas half of the genes of HUT14 cells did. These results indicate that one allele of the aortic smooth muscle actin gene in HUT14 cells has a transition point mutation (C----T) at codon 309 and that the amino acid sequences of normal human aorta and bovine smooth muscle actins are probably identical. In addition to the five introns interrupting exons at codons 150, 204, and 267, and between codons 41 and 42 and 327 and 328, which are common to skeletal muscle and cardiac muscle actin genes, the smooth muscle actin gene has two more intron sites between codons 84 and 85 and 121 and 122. The previously unreported intron site between codons 84 and 85 is unique to the smooth muscle actin gene. The intron site between codons 121 and 122 is common to beta-actin genes but is not found in other muscle actin genes. A hypothesis is proposed for the evolutionary pathway of the actin gene family.
Mol Cell Biol 1984 Jun
PMID:Structure of a human smooth muscle actin gene (aortic type) with a unique intron site. 633 May 28

In order to facilitate investigation of the cells responsible for overproduction of type VI collagen in the extracellular matrix surrounding the capillaries of diabetic rat myocardium, procedures have been developed for the isolation from this tissue of endothelial cells as well as a cell type identified as pericytes. This was accomplished by enzymatic and mechanical disruption of ventricles from young rats (125 g) followed by removal of myocytes through their nonadherence to tissue culture surfaces. Endothelial cells were separated by fluorescence-activated cell sorting after staining with rhodamine-labeled acetylated low density lipoprotein and were identified by their monolayer growth pattern, reaction with anti-von Willebrand factor and the ability to form capillary-like tubes induced by low serum concentration. Pericytes were purified by selective scraping for removal of other cell types and were identified by their irregular shape, overlapping growth pattern at confluence, reaction with anti-smooth muscle actin and content of GLUT4 glucose transporter. Fibroblasts, visualized after staining with rhodamine-labeled alpha 2-macroglobulin, were only rarely detected. Analysis of collagen by immunoblotting indicated formation by both cell types of alpha 1(IV) collagen as well as the three subunits of type VI (alpha 3 at 205 kDa and alpha 1 plus alpha 2 at 150 kDa). Both endothelial cells and pericytes demonstrated transcripts for types VI, IV and I collagen, as well as fibronectin, but while the level of the mRNA for type IV collagen was higher in pericytes than in endothelial cells, the reverse was true for collagens VI and I and fibronectin. These observations suggest that both endothelial cells and pericytes contribute to formation of the myocardial capillary matrix, but that changes involving only type VI collagen, such as occur in diabetic cardiomyopathy, may reflect a response primarily of endothelial cells.
J Mol Cell Cardiol 1995 May
PMID:Isolation of rat heart endothelial cells and pericytes: evaluation of their role in the formation of extracellular matrix components. 747 75

We have constructed a 2.0 centiMorgan (cM) resolution genetic linkage map for chromosome 15q that contains 55 polymorphic satellites and 3 RFLPs that have placed on the map with odds for order of at least 1,000:1. Genotypes from 67 polymorphic loci (64 polymorphic microsatellites) were used to construct the map. Nine genes are included in the 1,000:1 map and 37 markers have heterozygosities of at least 70%. The sex-equal map length is 128 cM and the largest genetic interval is 11 cM (15.5 cM on the female map). The female and male map lengths are 150 cM and 106 cM, respectively. The map was constructed with 'MultiMap' and is based on the CEPH reference pedigrees and includes over 12,000 new genotypes. A sub-set of 12 markers spanning the length of the linkage map were genotyped in a somatic cell hybrid panel with breakpoints that divided 15q into five segments. Cytogenetic placement agreed with the linkage positions for each of the microsatellites tested with the exception of one (ACTC) which failed to give consistent results. Ten spontaneous new mutations were identified from a subset of 42 polymorphic microsatellites (out of a total of 20,420 transmissions), giving an apparent observed spontaneous mutation rate of 5 x 10(-4) per locus. An integrated map of chromosome 15q was also constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. The sex average map spans 144.7 cM with an average distance between unique map locations of 3.5 cM and a maximum intermarker distance of 11.5 cM. These genetic linkage maps can be considered baseline maps for 15q which will be useful for physical mapping and the localization of disease genes and other genes of interest.
Hum Mol Genet 1993 Dec
PMID:A linkage map of human chromosome 15 with an average resolution of 2 cM and containing 55 polymorphic microsatellites. 790 87

The obstruction of the bladder outlet induces a marked increase in bladder mass, and this is accompanied by reduced contractility of bladder smooth muscle and alteration in the cellular architecture. In this study, we show that the composition of various isoforms of actin, a major component of the contractile apparatus and the cytoskeletal structure of smooth muscle, is altered in response to the obstruction-induced bladder hypertrophy. Northern blot analysis of the total RNA isolated from hypertrophied urinary bladder muscle, using a cDNA probe specific for smooth muscle gamma-actin, shows over 200% increase in the gamma-actin mRNA. However, the estimate of the amount of actin from the 2D gel reveals only a 16% increase in gamma-actin, since the 2D gel electrophoresis does not distinguish gamma-smooth muscle actin from gamma-cytoplasmic actin. The bladder smooth muscle alpha-actin and the smooth muscle alpha-actin mRNA are not altered in response to the hypertrophy. The obstructed bladder also reveals a decrease in the beta-cytoplasmic actin (37%) and a concomitant diminution in the beta-cytoplasmic actin mRNA (29%). Hence, the composition of the actin isoforms in bladder smooth muscle is altered in response to the obstruction-induced hypertrophy. This alteration of the actin isoforms is observed at both the protein and mRNA levels.
Mol Cell Biochem 1994 Feb 23
PMID:Alterations in the expression of the beta-cytoplasmic and the gamma-smooth muscle actins in hypertrophied urinary bladder smooth muscle. 803 76

Transforming growth factor-beta (TGF beta 1) and tumor necrosis factor alpha (TNF alpha) stimulate the transdifferentiation of fat-storing cells (FSC) in the rat liver into highly active and "synthetic" myofibroblast-like cells (MFBIC). This activation has been documented by differential-interference contrast and light microscopy using morphologic criteria (a reduction in the number and size of fat droplets, cell flattening and the development of long cytoplasmic extensions), by the loss of retinyl-palmitate (measured by HPLC) and by the enhanced expression of iso-alpha smooth muscle actin (demonstrated by immunofluorescence microscopy). Furthermore, while cell growth measured by the cell count and DNA content is slightly inhibited by TGF beta 1 (0.81 of the control), the combination of TGF beta 1 with TNF alpha stimulates cell proliferation to 1.44 times of the control. In addition the combination of TGF beta and TNF alpha potentiated the stimulatory effect on fibronectin synthesis (TGF beta alone: 1.4 times control; TNF alpha alone: 2.2 times control; TGF beta plus TNF alpha: 4.7 times control). The total protein synthesis was not altered by TGF beta or TNF alpha. In summary the results obtained identify TGF beta and TNF alpha as mediators stimulating key events in liver fibrogenesis (i.e. FSC proliferation, FSC transdifferentiation into MFBIC, and fibronectin synthesis).
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF beta 1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts. 809 22


1 2 3 4 5 6 7 8 9 10 Next >>