Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anthracyclines are effective cancer chemotherapeutic agents but can induce serious cardiotoxicity. Understanding the mechanism of cardiac damage by these agents will help in development of better therapeutic strategies against cancer. The GATA-4 transcription factor is an important regulator of cardiac muscle cells. The present study demonstrates that anthracyclines can down-regulate GATA-4 activity. Treatment of HL-1 cardiac muscle cells or isolated adult rat ventricular myocytes with anthracyclines such as daunorubicin and doxorubicin decreased the level of GATA-4 DNA-binding activity. The mechanism of decreased GATA-4 activity acts at the level of the GATA-4 gene, because anthracyclines caused significantly decreased levels of GATA-4 protein and mRNA. The rate of decline in GATA-4 transcript levels in the presence of actinomycin D was unaltered by anthracyclines, indicating that these agents may affect directly GATA-4 gene transcription. To determine whether decreased GATA-4 levels are functionally related to cardiac muscle cell death that can be induced by anthracyclines, the ability of ectopic GATA factors to rescue anthracycline-induced apoptosis was tested. Adenovirus-mediated expression of either GATA-4 or GATA-6 was sufficient to attenuate the incidence of apoptosis. Furthermore, suppression of GATA-4 DNA-binding activity by a dominant negative mutant of GATA-4 induced the apoptosis. These results suggest that the mechanism of anthracycline-induced cardiotoxicity may involve the down-regulation of GATA-4 and the induction of apoptosis.
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PMID:Anthracycline-induced suppression of GATA-4 transcription factor: implication in the regulation of cardiac myocyte apoptosis. 1252 8

Rab1 GTPase coordinates vesicle-mediated protein transport specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. We recently demonstrated that Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in HEK293 cells and that transgenic mice overexpressing Rab1 in the myocardium develop cardiac hypertrophy. To expand these studies, we determined in this report whether the modification of Rab1-mediated ER-to-Golgi transport can alter the cell surface expression and function of endogenous AT1R and AT1R-mediated hypertrophic growth in primary cultures of neonatal rat ventricular myocytes. Adenovirus-mediated gene transfer of wild-type Rab1 (Rab1WT) significantly increased cell surface expression of endogenous AT1R in neonatal cardiomyocytes, whereas the dominant-negative mutant Rab1N124I had the opposite effect. Brefeldin A treatment blocked the Rab1WT-induced increase in AT1R cell surface expression. Fluorescence analysis of the subcellular localization of AT1R revealed that Rab1 regulated AT1R transport specifically from the ER to the Golgi in HL-1 cardiomyocytes. Consistent with their effects on AT1R export, Rab1WT and Rab1N124I differentially modified the AT1R-mediated activation of ERK1/2 and its upstream kinase MEK1. More importantly, adenovirus-mediated expression of Rab1N124I markedly attenuated the Ang II-stimulated hypertrophic growth as measured by protein synthesis, cell size, and sarcomeric organization in neonatal cardiomyocytes. In contrast, Rab1WT expression augmented the Ang II-mediated hypertrophic response. These data strongly indicate that AT1R function in cardiomyocytes can be modulated through manipulating AT1R traffic from the ER to the Golgi and provide the first evidence implicating the ER-to-Golgi transport as a regulatory site for control of cardiomyocyte growth.
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PMID:Regulation of the cell surface expression and function of angiotensin II type 1 receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac myocytes. 1525 15

As coxsackievirus B3 (CoxB3) and adenoviruses may cause acute myocarditis and inflammatory cardiomyopathy, isolation of the common coxsackievirus-adenovirus-receptor (CAR) has provided an interesting new target for molecular antiviral therapy. Whereas many viruses show high mutation rates enabling them to develop escape mutants, mutations of their cellular virus receptors are far less likely. We report on antiviral efficacies of CAR gene silencing by short hairpin (sh)RNAs in the cardiac-derived HL-1 cell line and in primary neonatal rat cardiomyocytes (PNCMs). Treatment with shRNA vectors mediating RNA interference against the CAR resulted in almost complete silencing of receptor expression both in HL-1 cells and PNCMs. Whereas CAR was silenced in HL-1 cells as early as 24 h after vector treatment, its downregulation in PNCMs did not become significant before day 6. CAR knockout resulted in inhibition of CoxB3 infections by up to 97% in HL-1 cells and up to 90% in PNCMs. Adenovirus was inhibited by only 75% in HL-1 cells, but up to 92% in PNCMs. We conclude that CAR knockout by shRNA vectors is efficient against CoxB3 and adenovirus in primary cardiac cells, but the efficacy of this approach in vivo may be influenced by cell type-specific silencing kinetics in different tissues.
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PMID:Coxsackievirus B3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated RNA interference targeting their common receptor. 1737 97