Disease relevance of Acta1

• These cells, derived from a nitrosourea-induced mouse brain neoplasm, have some of the morphological characteristics of smooth muscle and have been shown to express the vascular smooth muscle isoform of alpha-actin [1].
• To investigate the therapeutic efficacy of Y-27632 in UUO kidneys, smooth muscle alpha actin (SMalphaA) expression, macrophage infiltration and fibrosis in the obstructed kidneys were studied [2].
• These results indicate that sustained overexpression of IGF-I in skeletal muscle elicits myofiber hypertrophy and provides the basis for manipulation of muscle physiology utilizing skeletal alpha-actin-based vectors [3].
• Cell cycle-mediated regulation of smooth muscle alpha-actin gene transcription in fibroblasts and vascular smooth muscle cells involves multiple adenovirus E1A-interacting cofactors [4].
• Four days after permanent coronary occlusion, the rates of myofibroblast (smooth muscle alpha-actin and BrdU double-positive) and endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 +/- 1.1% and 2.9 +/- 0.5%, respectively [5].

Psychiatry related information on Acta1

• Moreover, they demonstrate a potential role for class I bHLH factors and their inhibitors, Id and Twist, in SM alpha-actin regulation and suggest that these factors may play an important role in control of SMC differentiation and phenotypic modulation [6].

High impact information on Acta1

• To understand how DNA methylation affects tissue-specific activation of genes, we have transfected in vitro methylated alpha-actin (skeletal) constructs into fibroblasts, which do not produce endogenous alpha-actin, and into a myogenic line, which is inducible for alpha-actin expression [7].
• Vitelline vessels from null mice were deficient in smooth-muscle alpha-actin-expressing mesenchymal cells, which participate in organization of the vessel wall [8].
• We hypothesized that this CArG degeneracy contributes to cell-specific expression of smooth muscle alpha-actin in vivo, since substitution of c-fos consensus CArGs for the degenerate CArGs resulted in relaxed specificity in cultured cells [9].
• Using a carotid wire-injury model in mice carrying transgenes for smooth muscle alpha-actin, smooth muscle myosin heavy chain, or a SM22alpha promoter-beta-gal reporter, we collected arteries 7 and 14 days after injury and assessed changes in endogenous protein and mRNA levels and in beta-gal activity [10].
• The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold [11].

Chemical compound and disease context of Acta1

• As previously reported (I. Yano, I. Tomiyasu, S. Kitabatake, and K. Kaneda, Acta Leprologica 2:341-349, 1984), Nocardia rubra, one of the nonpathogenic actinomycetes, possesses three classes of mycolic acid-containing glycolipid, i.e., glucose mycolate, trehalose dimycolate, and trehalose monomycolate [12].
• As reported previously [Acta Neurobiol. Exp. 57 (1997) 263], palmitoylcarnitine was observed to promote differentiation of neuroblastoma NB-2a cells with a concomitant inhibition of proliferation and of the phorbol ester stimulated activity of the protein kinase C (PKC) [13].
• We previously reported that the induction of L-histidine decarboxylase (HDC) in mouse mastocytoma cells was synergistically potentiated with a combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) [Biochim. Biophys. Acta, 1133, 172-178 (1992)] [14].
• Nuclei from K21 murine mastocytoma cells do not form topoisomerase II-DNA adducts in response to amsacrine in the absence of a cytoplasmic factor tentatively identified as a type of casein kinase (Darkin, S.J. and Ralph, R.K. (1991) Biochim. Biophys. Acta 1088, 285-291) [15].
• Previous studies demonstrated that angiotensin II (Ang II)-induced hypertrophy of smooth muscle cells (SMCs) was associated with increased transcription of SM alpha-actin gene [16].

Biological context of Acta1

• Re-localization of Actsk-1 to mouse chromosome 8, a new region of homology with human chromosome 1 [17].
• We present here the genetic mapping of the alpha-skeletal actin locus (Actsk-1) on mouse Chromosome (Chr) 8, on the basis of the PCR analysis of a microsatellite in an interspecific backcross [17].
• Activation of the SRF-regulated immediate early genes Egr-1 and c-fos, as well as the alpha-Actin gene, is severely impaired [18].
• The complete nucleotide sequence of a genomic clone encoding the mouse skeletal alpha-actin gene has been determined [19].
• The complete sequence of the mouse skeletal alpha-actin gene reveals several conserved and inverted repeat sequences outside of the protein-coding region [19].

Anatomical context of Acta1

• Detailed comparison of their promoter sequences, as well as those of the cardiac and skeletal muscle alpha-actin genes, reveals a number of common elements [20].
• RESULTS: ISMCs expressed smooth muscle alpha-actin before and after IFN-gamma exposure [21].
• We have introduced the chicken genes for cytoplasmic beta-actin, cardiac alpha-actin, and skeletal alpha-actin into C2 cells, a murine myogenic cell line, and into L cells by using the simian virus 40-derived vector PSV2 -gpt [22].
• Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC 1.14.99.5) in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264] [23].
• However, this additional proliferative growth is not reflected in abnormal myocyte maturation, as assessed by the expression of the cardiac and skeletal isoforms of alpha-actin [24].

Associations of Acta1 with chemical compounds

• The skeletal alpha-actin gene is expressed poorly in pre- and post-fusion C2 cells, displaying no induction with differentiation [22].
• Muscles lacking SRF had very low levels of muscle creatine kinase and skeletal alpha-actin (SKA) transcripts and displayed other alterations to the gene expression program, indicating an overall immaturity of mutant muscles [25].
• Cytochalasin D and latrunculin B, inhibitors of actin polymerization, significantly reduced RhoA-induced activation of the alpha-actin promoter [26].
• Activation of the alpha-actin promoter by RhoA is greatly potentiated (up to 15-fold) by co-expression of the integrin beta1A or beta1D isoform but is significantly reduced by 70% with a co-expressed dominant negative mutant of beta1 integrin [26].
• Although the VSM alpha-actin promoter exhibits at least three similar sequence elements, it remained refractory to serum and cycloheximide induction [27].

Physical interactions of Acta1

• Nucleoprotein interactions governing cell type-dependent repression of the mouse smooth muscle alpha-actin promoter by single-stranded DNA-binding proteins Pur alpha and Pur beta [28].
• Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter [29].
• Herein, the ability of the adenovirus E1A 12 S protein to bind and functionally inactivate specific cell regulatory factors has been exploited to identify several previously unknown coactivators of the mouse smooth muscle alpha-actin promoter in rodent fibroblasts and vascular smooth muscle cells [4].

Regulatory relationships of Acta1

• The present study demonstrates a significant functional correlation between alpha-actin isoform content and cardiac contractile function and also that alpha-skeletal actin may promote an increased contractile function in the heart compared with alpha-cardiac actin [30].
• TGFbeta induces expression of smooth muscle alpha actin (SMalphaA) and incorporation into in stress fibers, a phenotype of differentiated myofibroblasts [31].
• These findings support the hypothesis that Pur alpha and Pur beta repress smooth muscle alpha-actin gene transcription by means of DNA strand-selective cis-element binding and cell type-dependent protein-protein interactions [28].
• Induction of vascular smooth muscle alpha-actin gene transcription in transforming growth factor beta1-activated myofibroblasts mediated by dynamic interplay between the Pur repressor proteins and Sp1/Smad coactivators [32].
• There was reduced alpha-actin expression in KO HC mice 7 days after injury that was partially inhibited by VCAM-1 antibody treatment [33].

Other interactions of Acta1

• Linkage of Agt and Actsk-1 to distal mouse chromosome 8 loci: a new conserved linkage [34].
• 5. In the latter case M-cadherin expression appears co-ordinately with that of myogenin and cardiac alpha-actin [35].
• Fourth arch artery maturation was studied with antibodies directed against smooth muscle alpha-actin and neural NCAM-1 and RMO-270 [36].
• Carnitine-deficient jvs mice expressed reduced levels of a group of genes which are preferentially expressed in the liver, including urea cycle enzyme genes (Biochim. Biophys. Acta 1138, 167-171, 1992) [37].
• In old Scn5a+/- mice, fibrosis was accompanied by heterogeneous expression of connexin 43 and upregulation of hypertrophic markers, including beta-MHC and skeletal alpha-actin [38].

Analytical, diagnostic and therapeutic context of Acta1

• In contrast, quantitative analysis of the alpha-actin-positive area showed a significant increase in the contribution of smooth muscle cells within the neointima in allografts from NOS2 -/- recipients (28.2+/-2.0%) compared with wild-type controls (13.2+/-2.3%; P<.0001) [39].
• Northern blot analysis showed an increase of cardiac alpha-actin mRNA and a decrease of T alpha-globin mRNA expression, providing further evidence of a conversion from ventral to dorsal phenotype [40].
• Electron microscopy and ICC for alpha-actin, fibronectin, and vimentin identified this multicellular layer of periductal cells as differentiated fibroblasts [41].
• A down-regulation of alpha-actin isoform was observed by immunofluorescence and immunoblotting analysis using a specific monoclonal antibody [42].
• Denervation stimulated DHPR gene expression less than 0.6-fold, despite 8-fold upregulation of delta-subunit mRNA and reciprocal effects on the skeletal and cardiac alpha-actin genes [43].

References