University of Kentucky

About: University of Kentucky is a education organization based out in Lexington, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 43933 authors who have published 92195 publications receiving 3256087 citations. The organization is also known as: UK.

Na/K-ATPase Y260 Phosphorylation-mediated Src Regulation in Control of Aerobic Glycolysis and Tumor Growth

Abstract: We report here the identification of α1 Na/K-ATPase as a major regulator of the proto-oncogene Src kinase and the role of this regulation in control of Warburg effect and tumor growth. Specifically, we discovered Y260 in α1 Na/K-ATPase as a Src-specific phosphorylation and binding site and that Y260 phosphorylation is required for Src-mediated signal transduction in response to a number of stimuli including EGF. As such, it enables a dynamic control of aerobic glycolysis. However, such regulation appears to be lost or attenuated in human cancers as the expression of Na/K-ATPase α1 was significantly decreased in prostate, breast and kidney cancers, and further reduced in corresponding metastatic lesions in patient samples. Consistently, knockdown of α1 Na/K-ATPase led to a further increase in lactate production and the growth of tumor xenograft. These findings suggest that α1 Na/K-ATPase works as a tumor suppressor and that a loss of Na/K-ATPase-mediated Src regulation may lead to Warburg phenotype in cancer.

Productivity Is a Poor Predictor of Plant Species Richness

Abstract: For more than 30 years, the relationship between net primary productivity and species richness has generated intense debate in ecology about the processes regulating local diversity. The original view, which is still widely accepted, holds that the relationship is hump-shaped, with richness first rising and then declining with increasing productivity. Although recent meta-analyses questioned the generality of hump-shaped patterns, these syntheses have been criticized for failing to account for methodological differences among studies. We addressed such concerns by conducting standardized sampling in 48 herbaceous-dominated plant communities on five continents. We found no clear relationship between productivity and fine-scale (meters−2) richness within sites, within regions, or across the globe. Ecologists should focus on fresh, mechanistic approaches to understanding the multivariate links between productivity and richness.

Dysfunctional HDL and atherosclerotic cardiovascular disease

Abstract: High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.

α1-Adrenergic Receptor Subtypes Molecular Structure, Function, and Signaling

Abstract: The α1ARs are important mediators of sympathetic nervous system responses, particularly those involved in cardiovascular homeostasis, such as arteriolar smooth muscle constriction and cardiac contraction.1 2 In addition, α1ARs have more recently been implicated in the pathogenesis of cardiac hypertrophy, in ischemia-induced cardiac arrhythmias, and in ischemic preconditioning.1 3 Like other ARs, α1ARs are activated by the catecholamines, norepinephrine and epinephrine. They are intrinsic membrane glycoproteins and are members of the GPCR superfamily. Over the past 10 to 15 years, data initially based on functional, radioligand, and biochemical studies have accumulated, indicating that the α1ARs are a heterogeneous group of distinct but related proteins. This conclusion has been confirmed with the molecular cloning of three distinct α1-receptor subtypes, although until recently discrepancies between the properties of the cloned expressed receptors and those characterized pharmacologically and biochemically have led to confusion in the classification of α1-receptor subtypes and their coupled effector responses. As detailed in the present review, much of this confusion has now been clarified for the three cloned α1ARs. These and other recent insights into the molecular structure, function, and signaling of α1ARs, the control of α1AR-gene expression, and pharmacological evidence for additional α1AR subtypes will be reviewed here. For additional information, the reader is also referred to several previous reviews of α1ARs.4 5 6 7 Functional studies of AR responses, particularly from the laboratories of McGrath8 and Ruffolo,9 provided the initial evidence that there may be subtypes of α1ARs. These studies indicated that postjunctional responses mediated by α1ARs could not be explained adequately on the basis of a single population of receptors. This concept was further advanced …