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Comparative molecular field analysis (CoMFA) was used to analyze the relationship between the structure of a group of ryanoids and the modulation of the calcium channel function of the ryanodine receptor. The conductance properties of ryanodine receptors purified from sheep heart were measured using the planar, lipid bilayer technique. The magnitude of the(More)
AIMS Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that contributes to pathogenic cardiac remodelling via mechanisms that involve oxidative stress. However, the direct impact of TGF-beta1 on contractile function of ventricular myocytes is incompletely understood. METHODS AND RESULTS Reactive oxygen species (ROS) production and(More)
OBJECTIVE Approximately 25% of children and adolescents with type 1 diabetes will develop diastolic dysfunction. This defect, which is characterized by an increase in time to cardiac relaxation, results in part from a reduction in the activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), the ATP-driven pump that translocates Ca(2+) from the(More)
AIMS Ventricular myocytes isolated from hearts of streptozotocin (STZ)-diabetic rats exhibit increased spontaneous Ca(2+) release. Studies attribute this defect to an enhancement in activity of type 2 ryanodine receptor (RyR2). To date, underlying reasons for RyR2 dysregulation remain undefined. This study assesses whether the responsiveness of RyR2(More)
Recent evidence suggests that a central mechanism may be contributing to the sympathetic abnormality in diabetes. Nitric oxide (NO) has been known as a neurotransmitter in the central nervous system. The goal of this study was to examine the role of the endogenous NO system of the paraventricular nucleus (PVN) in regulation of renal sympathetic nerve(More)
Decrease in cardiac contractility is a hallmark of chronic diabetes. Previously we showed that this defect results, at least in part, from a dysfunction of the type 2 ryanodine receptor calcium-release channel (RyR2). The mechanism(s) underlying RyR2 dysfunction is not fully understood. The present study was designed to determine whether non-cross-linking(More)
In a previous study, we showed that after 6 weeks of streptozotocin-induced diabetes (6D), expression of type 2 ryanodine receptor calcium-release channels (RyR2) did not change significantly in rat hearts. However, the ability of this protein to bind [3H]ryanodine was compromised. Loss in activity therefore resulted from diabetes-induced increases in(More)
OBJECTIVE Endothelial progenitor cells (EPCs) are decreased in number and function in type 2 diabetes. Mechanisms by which this dysfunction occurs are largely unknown. We tested the hypothesis that a chronic inflammatory environment leads to insulin signaling defects in EPCs and thereby reduces their survival. Modifying EPCs by a knockdown of nuclear(More)
1. Localized calcium release events (calcium sparks) were studied in voltage-clamped cut twitch fibres of Rana temporaria. 2. A histogram of thousands of spontaneous sparks displayed a monotonically decreasing amplitude distribution from the low to the high limit of > 7 DeltaF/F(0) units. 3. Several effects of low micromolar concentrations of ryanodine(More)
CD38 is a 45-kD ectoenzyme involved in the synthesis of potent calcium (Ca(2+))-mobilizing agents, cyclic adenosine diphosphate-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP+). In HIV-1-infected patients, increased CD38 expression on CD8+ T cells is linked to immune system activation and progression of HIV-1 infection. However,(More)