The half-life of c-myc mRNA is regulated when cells change their growth rates or differentiate. Two regions within c-myc mRNA determine its short half-life. One is in the 3′-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c-myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life. Here we report the cloning and further characterization of the mouse CRD-BP, a 577 amino acid protein containing four hnRNP K-homology domains, two RNP domains, an RGG RNA-binding domain and nuclear import and export signals. The CRD-BP is closely related to the chicken β-actin zipcode-binding protein and is similar to three other proteins, one of which is overexpressed in some human cancers. Recombinant mouse CRD-BP binds specifically to c-myc CRD RNA in vitro and reacts with antibody against human CRD-BP. Most of the CRD-BP in the cell is cytoplasmic and co-sediments with ribosomal subunits.
Background-We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury. Methods and Results-C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. Infarct size was measured using triphenyltetrazoliumchloride staining. A c-Jun NH 2 -terminal kinase (JNK) activation was determined by Western blotting, nuclear factor (NF)-B activity was detected by gel-shift assay, and cytokine expression was measured by ribonuclease protection assay.
Introduction-Historically, the treatment of anorectal melanoma has been abdominoperineal resection (APR) but more recently local resection alone. Although treatment at melanoma centers has become less aggressive in the modern era, the adoption of this approach and related outcomes across the United States is unknown.
Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab (Alexion Pharmaceuticals, Inc., Cheshire, CT, USA) is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms. Prospective, randomised, double-blind, placebo-controlled trials using pexelizumab during percutaneous coronary intervention following acute myocardial infarction (AMI), or in patients undergoing coronary artery bypass graft (CABG) with CPB, have demonstrated a reduction in morbidity and mortality. Thus, pexelizumab represents a promising therapeutic option with sustained benefit both in AMI and during CABG with CPB.
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