Novel approaches to determine the functional role of cardiomyocyte specific E3 ligase, Pellino-1 following myocardial infarction.

Objectives: Ubiquitination plays a vital role in controlling vascular inflammation, cellular protein quality control, and minimizing misfolded protein toxicity. Pellino-1 (Peli1), a type of E3 ubiquitin ligase, has emerged as a critical regulator of the innate immune response; however, its role in the repair and regeneration of ischemic myocardium remains to be elucidated.

Methods: Mice (8-12 weeks old, male and females) were divided into (i) Wild type (ii) cardiomyocyte-specific Peli1 overexpressed (AMPEL1), (iii) cardiomyocyte-specific Peli1 knockout (CP1KO) and were subjected to sham and left anterior descending artery ligation.

Inactivation influences the extent of inhibition of voltage-gated Ca channels by Gem-implications for channelopathies.

Voltage-gated Ca channels (VGCC) directly control muscle contraction and neurotransmitter release, and slower processes such as cell differentiation, migration, and death. They are potently inhibited by RGK GTP-ases (Rem, Rem2, Rad, and Gem/Kir), which decrease Ca channel membrane expression, as well as directly inhibit membrane-resident channels. The mechanisms of membrane-resident channel inhibition are difficult to study because RGK-overexpression causes complete or near complete channel inhibition.

Protective Effect of Cardiomyocyte-Specific Prolyl-4-Hydroxylase 2 Inhibition on Ischemic Injury in a Mouse MI Model.

Background: Our earlier studies showed that inhibiting prolyl-4-hydroxylase enzymes (PHD-1 and PHD-3) improves angiogenesis, heart function, and limb perfusion in mouse models via stabilizing hypoxia-inducible transcription factor-alpha (HIF-1α). The present study explored the effects of the prolyl-4-hydroxylase enzyme, PHD-2, on ischemic heart failure using cardiac-specific PHD-2 gene knockout (KO) mice (PHD2 -/- ).

Study Design: Adult wild-type (WT) and PHD2 -/- mice, 8-12 weeks old, were subjected to myocardial infarction (MI) by irreversibly ligating the left anterior descending (LAD) coronary artery.

The molecular determinants of R-roscovitine block of hERG channels.

Human ether-à-go-go-related gene (Kv11.1, or hERG) is a potassium channel that conducts the delayed rectifier potassium current (IKr) during the repolarization phase of cardiac action potentials. hERG channels have a larger pore than other K+channels and can trap many unintended drugs, often resulting in acquired LQTS (aLQTS).