Qingyou Du

Bio: Qingyou Du is an academic researcher from University of Dundee. The author has contributed to research in topics: Sulfonylurea receptor & Dictyostelium discoideum. The author has an hindex of 15, co-authored 31 publications receiving 481 citations.

Glyceraldehyde 3-phosphate dehydrogenase serves as an accessory protein of the cardiac sarcolemmal K(ATP) channel.

Abstract: Cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels, composed of Kir6.2 and SUR2A subunits, are regulated by intracellular ATP and they couple the metabolic status of the cell with the membrane excitability. On the basis of previous studies, we have suggested that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) may be a part of the sarcolemmal K(ATP)-channel protein complex. A polypeptide of approximately 42 kDa was immunoprecipitated with an anti-SUR2A antibody from guinea-pig cardiac membrane fraction and identified as GAPDH. Immunoprecipitation/western blotting analysis with anti-Kir6.2, anti-SUR2A and anti-GAPDH antibodies showed that GAPDH is a part of the sarcolemmal K(ATP)-channel protein complex in vivo. Further studies with immunoprecipitation/western blotting and the membrane yeast two-hybrid system showed that GAPDH associates physically with the Kir6.2 but not the SUR2A subunit. Patch-clamp electrophysiology showed that GAPDH regulates K(ATP)-channel activity irrespective of high intracellular ATP, by producing 1,3-bisphosphoglycerate, a K(ATP)-channel opener. These results suggest that GAPDH is an integral part of the sarcolemmal K(ATP)-channel protein complex, where it couples glycolysis with the K(ATP)-channel activity.

Prostaglandins and Inflammation

Abstract: Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase isoenzymes, and their biosynthesis is blocked by nonsteroidal antiinflammatory drugs, including those selective for inhibition of cyclooxygenase-2. Despite the clinical efficacy of nonsteroidal antiinflammatory drugs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm.

Naturally occurring p16 Ink4a -positive cells shorten healthy lifespan

Abstract: Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

Anticonvulsant mechanisms of the ketogenic diet.

Abstract: The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD may exert its anticonvulsant activity against the backdrop of several seemingly disparate mechanistic theories. We summarize key insights gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control. Chronic ketosis is anticipated to modify the tricarboxcylic acid cycle to increase GABA synthesis in brain, limit reactive oxygen species (ROS) generation, and boost energy production in brain tissue. Among several direct neuro-inhibitory actions, polyunsaturated fatty acids increased after KD induce the expression of neuronal uncoupling proteins (UCPs), a collective up-regulation of numerous energy metabolism genes, and mitochondrial biogenesis. These effects further limit ROS generation and increase energy production. As a result of limited glucose and enhanced oxidative phosphorylation, reduced glycolytic flux is hypothesized to activate metabolic K(ATP) channels and hyperpolarize neurons and/or glia. Although it is unlikely that a single mechanism, however well substantiated, will explain all of the diet's clinical benefits, these diverse, coordinated changes seem poised to stabilize synaptic function and increase the resistance to seizures throughout the brain.

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Abstract: It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists ( ). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP2 receptor, also termed CRTH2, has little structural resemblance to DP1 and other receptors described in the original prostanoid receptor classification. DP2 receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A2 heterodimeric receptors for 8- epi -prostaglandin E2, wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities.

Methods Molecular Biology

Abstract: For over 35 years, biological scientists have come to rely on the research protocols and methodologies in the critically acclaimed Methods in Molecular Biology series. The series was the first to introduce the step-by-step protocols approach that has become the standard in all biomedical protocol publishing. Each protocol is provided in readilyreproducible step-bystep fashion, opening with an introductory overview, a list of the materials and reagents needed to complete the experiment, and followed by a detailed procedure that is supported with a helpful notes section offering tips and tricks of the trade as well as troubleshooting advice. These hallmark features were introduced by series editor Dr. John Walker and constitute the key ingredient in each and every volume of the Methods in Molecular Biology series. Tested and trusted, comprehensive and reliable, all protocols from the series are indexed in PubMed.