DSpace Collection:

Mutations of the ca²⁺-sensing stromal interaction molecule stim1 regulate ca²⁺ influx by altered oligomerization of stim1 and by destabilization of the ca²⁺ channel orai1

2013-06-17T04:30:50Z

Title: Mutations of the ca²⁺-sensing stromal interaction molecule stim1 regulate ca²⁺ influx by altered oligomerization of stim1 and by destabilization of the ca²⁺ channel orai1 Author: Kilch, Tatiana; Alansary, Dalia; Peglow, Martin; Dorr, Kathrin; Rychkov, Grigori; Rieger, Heiko; Peinelt, Christine; Niemeyer, Barbara A. Abstract: A drop of endoplasmic reticulum Ca²⁺ concentration triggers its Ca²⁺ ssensor protein stromal interaction molecule 1 (STIM1) to oligomerize and accumulate within endoplasmic reticulum-plasma membrane junctions where it activates Orai1 channels, providing store-operated Ca²⁺ entry. To elucidate the functional significance of N-glycosylation sites of STIM1, we created different mutations of asparagine-131 and asparagine-171. STIM1 NN/DQ resulted in a strong gain of function. Patch clamp, Total Internal Reflection Fluorescent (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) analyses revealed that expression of STIM1 DQ mutants increases the number of active Orai1 channels and the rate of STIM1 translocation to endoplasmic reticulum-plasma membrane junctions with a decrease in current latency. Surprisingly, co-expression of STIM1 DQ decreased Orai1 protein, altering the STIM1:Orai1 stoichiometry. We describe a novel mathematical tool to delineate the effects of altered STIM1 or Orai1 diffusion parameters from stoichiometrical changes. The mutant uncovers a novel mechanism whereby “superactive” STIM1 DQ leads to altered oligomerization rate constants and to degradation of Orai1 with a change in stoichiometry of activator (STIM1) to effector (Orai1) ratio leading to altered Ca²⁺ homeostasis.

Effects of a high protein diet on body weight and comorbidities associated with obesity

2013-05-27T06:30:36Z

Title: Effects of a high protein diet on body weight and comorbidities associated with obesity Author: Clifton, Peter Marshall Abstract: Red meat intake has been frequently associated with the development of coronary artery disease and type 2 diabetes but vegetable protein has been associated with protection from these diseases. Whether this is related to the protein per se or to the increased polyunsaturated fat or higher fibre levels associated with more vegetarian diets is not clear. High protein diets are associated with greater satiety and in some studies are associated with greater weight loss compared with high carbohydrate diets especially in an ad libitum design. These diets also lower plasma triglyceride and blood pressure and sometimes spare lean mass. There appear to be no harmful effects of high protein diets on bone density or renal function in weight loss studies.

MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

2013-06-11T04:46:30Z

Title: MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss Author: McIver, Cassandra Monique; Wycherley, Thomas Philip; Clifton, Peter Marshall Abstract: Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle) mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy) in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. This review evaluates the relationship between the macronutrient composition of calorie restricted diets and weight loss using metabolic indicators. Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP) and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1. Description: Extent: 8p.

Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial

2013-06-11T04:38:47Z

Title: Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial Author: Coles, Leah; Clifton, Peter Marshall Abstract: Background: The consumption of beetroot juice on a low nitrate diet may lower blood pressure (BP) and therefore reduce the risk of cardiovascular events. However, it is unknown if its inclusion as part of a normal diet has a similar effect on BP. The aim of the study was to conduct a randomized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP. Method: Fifteen women and fifteen men participated in a double-blind, randomized, placebo-controlled, crossover study. Volunteers were randomized to receive 500 g of beetroot and apple juice (BJ) or a placebo juice (PL). Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor (ABPM). Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities. The identical procedure was repeated 2-wk later with the drink (BJ or PL) not consumed on the first visit. Results: Overall, there was a trend (P=0.064) to lower systolic blood pressure (SBP) at 6-h after drinking BJ relative to PL. Analysis in men only (n=13) after adjustment for baseline differences demonstrated a significant (P<0.05) reduction in SBP of 4 – 5 mmHg at 6-h after drinking BJ. Conclusions: Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults. Description: Extent: 6p.