Disease relevance of Acta1

• Thus, smooth muscle alpha-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal alpha-actin [1].
• This alpha-actin was hardly detected at all in the transformants induced by Rous sarcoma virus, v-H-ras oncogene or adenovirus type 12, while the alpha-actin was retained in the transformed cell lines induced by N-methyl-N'-nitro-N-nitrosoguanidine or in SV40, which are cell lines of relatively low malignancy [2].
• A normal rat fibroblast 3Y1 cell line expresses smooth muscle a actin and the expression of alpha actin is suppressed in the transformant (SR-3Y1-2) induced by a Raus sarcoma virus [3].
• Gene transfer with smooth muscle alpha actin into the SR-3Y1-2 cell line reduced growth and invasiveness in vitro, as well as tumor growth and experimental lung metastasis depending on the expression of the alpha actin [3].
• It is likely that this represents the in vivo mechanism, as well, since extracts from L8 myoblasts specifically demethylate an alpha-actin gene, while extracts from F9 teratocarcinoma cells specifically demodify the Aprt CpG island [4].

Psychiatry related information on Acta1

• Although Id mRNA becomes undetectable in adult ventricular myocytes 48 h following isolation in the absence of serum, it can be rapidly reinduced by an alpha-adrenergic agonist, accompanied by increased protein synthesis and the reexpression, in defined media, of the neonatal genes prepro-ANP and skeletal muscle alpha-actin [5].

High impact information on Acta1

• Transient transfection into L8 myoblasts has been used to study the rat alpha-actin gene promoter [6].
• Dynamics of demethylation and activation of the alpha-actin gene in myoblasts [6].
• DMSO (2%) inhibits the fusion of myoblasts to form multinucleate myotubes, the normal increases in activity of creatine phosphokinase (CPK) and acetylcholinesterase, and the synthesis of alpha-actin and acetylcholine receptor protein [7].
• The strong conservation of these sequences suggests that they may have a role in the tissue-specific expression of the skeletal muscle alpha-actin gene [8].
• Differentiation of muscle cells is characterized morphologically by the acquisition of contractile filaments and characteristic shape changes, and on the molecular level by induction of the expression of several genes, including those for the muscle-specific alpha-actin isoforms [9].

Chemical compound and disease context of Acta1

• RNA analyses indicate that ventricles of clenbuterol-treated rats express elevated levels of mRNA to atrial natriuretic factor without a concomitant increase in skeletal alpha-actin and beta-myosin heavy chain, consistent with a "physiological" form of cardiac hypertrophy [10].
• Ang II induced "late" markers for cardiac hypertrophy, skeletal alpha-actin and atrial natriuretic factor expression, within 6 hours in myocytes [11].
• In addition, the expression levels of skeletal alpha-actin, beta-myosin heavy chain, and ANP genes, markers of hypertrophy, were partially elevated by treatment with HS-142-1 (100 microg/mL) under nonstimulated or PE-stimulated conditions [12].
• Thus the electrophoretically fast ferritin resembles that reported by Massover [(1985) Biochim. Biophys. Acta 829, 377-386] in livers of mice with short-term parenteral iron overload [13].
• We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. d-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin [14].

Biological context of Acta1

• Expression of vascular smooth muscle alpha-actin, the earliest alpha-actin induced during cardiac myogenesis, was increased by all three growth factors [15].
• Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle alpha-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle alpha-actin (r = 0.532; P = 0.009); P less than 0.0005 for the difference in the correlation coefficients [1].
• These data indicate that cell cycle withdrawal is not a prerequisite for the induction of SM alpha actin synthesis in SMC at confluency [16].
• Since confluent cells exhibit contact inhibition of growth, this finding suggests that induction of SM alpha actin may be associated with cell cycle withdrawal [16].
• Nuclear run-on analysis and transfection studies indicated that the effects of Ang II on SM alpha-actin were mediated at least in part at the transcriptional level [17].

Anatomical context of Acta1

• In hypertrophied hearts, the prevalence of smooth muscle alpha-actin gene induction was 0.909, versus 0.545 for skeletal muscle alpha-actin (P less than 0.05) [1].
• Cultured smooth muscle cells (SMC) undergo induction of smooth muscle (SM) alpha actin at confluency [16].
• The changes in morphology and function were accompanied by a marked increase in beta-myosin heavy chain isoform transcription in cocultured myocytes, a return to the ratio of cardiac to skeletal alpha-actin expected in adult rat myocardium, and a much reduced expression of smooth muscle alpha-actin [18].
• A monoclonal antibody against smooth muscle alpha-actin (SM alpha-actin) was used to study the expression of SM alpha-actin in kidney sections and mesangial cell (MC) cultures [19].
• In the tissue sections, indirect immunofluorescence revealed intense labeling of vascular smooth muscle cells and precapillary pericytes for SM alpha-actin [19].

Associations of Acta1 with chemical compounds

• These results provide evidence for involvement of a homeodomain transcription factor, MHox, in Ang II-mediated stimulation of SM alpha-actin via a CArG/SRF-dependent mechanism [17].
• The objective of the present study was to examine the molecular mechanisms whereby angiotensin II (Ang II) stimulates smooth muscle (SM) alpha-actin expression in rat aortic smooth muscle cells (SMCs) [17].
• In addition, U0126 completely normalized ANF gene expression, but did not affect or only marginally affected expression of MHC and alpha-actin isoforms [20].
• Cholera toxin (CTX; 10 nM) treatment lead to a large and sustained increase in the cyclic AMP concentration after 2 h which correlated with change of VSMC morphology including complete disruption of the Sm alpha-actin filament array and loss of focal adhesions [21].
• Treatment of VSMCs with CTX did not influence tyrosine phosphorylation of p125(FAK) and paxillin but decreased the content of a Sm alpha-actin protein [21].

Co-localisations of Acta1

• Double staining procedures showed big endothelin-1 immunoreactivity to be co-localized with alpha-actin immunoreactivity [22].

Regulatory relationships of Acta1

• In summary, these results suggest a conserved role for CArG A, CArG B, and the TCE in TGF-beta-induced expression of SM alpha-actin in SMCs and non-SMCs that is modified by a complex interplay of positive- and negative-acting cis elements in a cell-specific manner [23].
• Combined in situ hybridization and immunocytochemistry reveals that most elastin mRNA-expressing cells in the media are alpha-actin-positive smooth muscle cells [24].
• Culture-induced SM alpha-actin expression was suppressed in the presence of LPS (> 5 ng/ml) and/or IFN gamma (> 1 U/ml) dose-dependently [25].
• The sequence spanning -894 to +1 of the SM alpha-actin promoter directed high levels of transcription that were attenuated in serum-restricted cells and upregulated upon treatment with serum or endothelin-1 [26].
• ET-3-induced [3H]leucine incorporation, skeletal alpha-actin mRNA and cell surface area were inhibited by a synthetic ETB receptor antagonist (BQ788) [27].

Other interactions of Acta1

• Acidic FGF (25 ng/ml) produced seven- to eightfold reciprocal changes in MHC expression but, unlike either TGF-beta 1 or basic FGF, inhibited both striated alpha-actin genes by 70-90% [15].
• In contrast, serum stimulation was shown to increase nonmuscle beta-actin mRNA level, whereas SM alpha-actin mRNA level remained constant [28].
• These data indicate that both JNKs and p38 participate in regulation of SM- alpha-actin expression [29].
• We found that regenerating muscle shows that embryonic pattern of alpha-actin mRNAs in the early stage and concluded that the recovery of alpha-skeletal actin mRNA expression to the adult pattern is influenced by innervation, while alpha-cardiac actin mRNA expression is nerve independent [30].
• Double-labeling with antibodies against proliferating cell nuclear antigen and SM alpha-actin revealed SM alpha-actin-positive filaments in both replicating and resting cells [19].

Analytical, diagnostic and therapeutic context of Acta1

• This issue was further examined in the present study using fluorescence-activated cell sorting of SMC undergoing induction at confluency and by examination of the effects of FBS and platelet-derived growth factor (PDGF) on SM alpha actin expression in postconfluent SMC cultures that had already undergone induction [16].
• Western and Northern blot analyses established that this alpha-actin was a smooth muscle alpha-isoform [2].
• An alpha-actin in addition to cytoplasmic beta- and gamma-actins was detected in 3Y1 by two-dimensional gel electrophoresis [2].
• The effects of aloe emodin on production of type I collagen and smooth muscle cell alpha-actin were examined at the same concentration, by quantitative immunoprecipitation [31].
• The cell phenotype was characterized by immunostaining and Western blot for alpha-actin and desmin [32].

References