Transgenic overexpression of ribonucleotide reductase improves cardiac performance

Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure.

AIMS Heart failure remains a leading cause of morbidity, hospitalizations, and deaths. We previously showed that overexpression of the enzyme ribonucleotide reductase (RNR) in cardiomyocytes increased levels of the myosin activator, 2-deoxy-ATP, catalysed enhanced contraction, and improved cardiac performance in rodent hearts. Here we used a swine model of myocardial infarction (MI) to test pre...

Ribonucleotide reductase in developing brain.

Ribonucleotide Reductase Inhibitors for Restenosis

Percutaneous transluminal coronary angioplasty (PTCA) has greatly benefited patients with occluded coronary arteries, but its benefits have been undermined by a high incidence of restenosis. The introduction of coronary stents has significantly improved the short and long term outcome but restenosis still occurs in approximately 15-30 % of patients within 6 months. Research efforts are now bein...

Broad overexpression of ribonucleotide reductase genes in mice specifically induces lung neoplasms.

Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in nucleotide biosynthesis and plays a central role in genome maintenance. Although a number of regulatory mechanisms govern RNR activity, the physiologic effect of RNR deregulation had not previously been examined in an animal model. We show here that overexpression of the small RNR subunit potently and selectively induces lung ne...

Investigation of solvent effect on the active site energy of Carbonic Anhydrase and Ribonucleotide Reductase

Enzymes catalyze many biological reactions. The rates of chemical reaction in the presence ofenzymes are, in some cases, accelerated more than 10 orders of magnitude relative to thecorresponding rates in solution.In this paper a comparison between optimized structures of two enzyme molecules in aspect ofenergy and dipole moment in different conditions including presence of metallic ion, without...