Identification of further important residues within the Glut4 carboxy-terminal tail which regulate subcellular trafficking

The insulin-responsive glucose transporter, Glut4, exhibits a unique subcellular distribution such that in the absence of insulin >95% of the protein is stored within intracellular membranes. In response to insulin, Glut4 exhibits a large mobilisation to the plasma membrane. Studies of the amino acid motifs which regulate the unique trafficking of Glut4 have identified several key residues within the soluble cytoplasmic N- and C-terminal domains of Glut4. Of particular note is a Leu-498Leu-499 motif within the C-terminal domain that has been proposed to regulate both internalisation from the plasma membrane and sorting to an insulin-sensitive compartment. In this study, we have examined the role of the adjacent amino acids (Glu-491, Gln-492 and Glu-493) by their sequential replacement with Ala. Our results are consistent with the notion that Glu-491 and Glu-493 play an important role in the sub-endosomal trafficking of Glut4, as substitution of these residues with Ala results in increased levels of these proteins at the cell surface, reduced insulin-stimulated translocation and increased susceptibility to endosomal ablation. These residues, together with other identified sequences within the C-terminus of Glut4, are likely to be crucial targeting elements that regulate Glut4 subcellular distribution.     

Water-storage capacity ofThuja,Tsuga andAcer stems measured by dehydration isotherms

Water-storage capacity was measured inThuja occidentalis L.,Tsuga canadensis (L.) Carr., andAcer saccharum Marsh. during the dehydration of stem segments 1.5–2.5 cm in diameter. Stem water potential was measured with a temperature-corrected stem hygrometer and cavitations were detected acoustically. Water loss was measured by weight change. Dehydration isotherms consistently displayed three phases. The first phase, from water potential (Ψ) 0 to about −0.2 MPa, had a high capacitance (C>0.4kg water lost· (1 of tissue)⁻¹· MPa⁻¹) and we have attributed this high C to capillary water as defined by Zimmermann (1983, Xylem structure and the ascent of sap, Springer-Verlag). The second phase from Ψ=−0.5 to about −2.0 had the lowest C values (<0.02 kg·l⁻¹·MPa⁻¹) and was accompanied by a few cavitation events. This phase may have been a transition zone between capillary storage and water released by cavitation events as well as water drawn from living cells of the bark. The third phase also had a high C (about 0.07–0.22kg·l⁻¹·MPa⁻¹) and was associated with many cavitation events while Ψ declined below about −2.5 MPa; we presume the high capacitance was the consequence of water released by cavitation events. We discuss the ecological adaptive advantage of these three phases of water-storage in trees. In moist environments, water withdrawn from capillary storage may be an important fraction of transpiration, but may be of little adaptive advantage. For most of the growth season trees draw mainly on elastic storage, but stem elastic storage is less than leaf elastic storage and therefore unlikely to be important. In very dry environments, water relased by cavitation events might be important to the short-term survival of trees.     

The emerging roles of lactate as a redox substrate and signaling molecule in adipose tissues

Journal of Physiology and Biochemistry - Thermogenic (brown and beige) adipose tissues improve glucose and lipid homeostasis and therefore represent putative targets to cure obesity and related...     

Aluminium in aquatic environments: abundance and ecotoxicological impacts

Aquatic Ecology - Aluminium (Al) is a common chemical element released into the aquatic environment from the Earth’s crust and many anthropogenic activities. It may be present in various...     

Terpenes from pittosporaceae

The monoterpenes of the fruits of Pittosporum resiniferum and P. undulatum have been identified. The essential oil of P. resiniferum contai     

Chicoric Acid Is an Antioxidant Molecule That Stimulates AMP Kinase Pathway in L6 Myotubes and Extends Lifespan in Caenorhabditis elegans

Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5–100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases.     

Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone

Human obesity is characterized by chronic low-grade inflammation in white adipose tissue and is often associated with hypertension. The potential induction of indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme in tryptophan/kynurenine degradation pathway, by proinflammatory cytokines, could be associated with these disorders but has remained unexplored in obesity. Using immunohistochemistry, we detected IDO1 expression in white adipose tissue of obese patients, and we focused on its contribution in the regulation of vascular tone and on its immunoregulatory effects. Concentrations of tryptophan and kynurenine were measured in sera of 36 obese and 15 lean women. The expression of IDO1 in corresponding omental and subcutaneous adipose tissues and liver was evaluated. Proinflammatory markers and T-cell subsets were analyzed in adipose tissue via the expression of CD14, IL-18, CD68, TNFα, CD3ε, FOXP3 [a regulatory T-cell (Treg) marker] and RORC (a Th17 marker). In obese subjects, the ratio of kynurenine to tryptophan, which reflects IDO1 activation, is higher than in lean subjects. Furthermore, IDO1 expression in both adipose tissues and liver is increased and is inversely correlated with arterial blood pressure. Inflammation is associated with a T-cell infiltration in obese adipose tissue, with predominance of Th17 in the omental compartment and of Treg in the subcutaneous depot. The Th17/Treg balance is decreased in subcutaneous fat and correlates with IDO1 activation. In contrast, in the omental compartment, despite IDO1 activation, the Th17/Treg balance control is impaired. Taken together, our results suggest that IDO1 activation represents a local compensatory mechanism to limit obesity-induced inflammation and hypertension.     

γ-Lactam-Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC₅₀ around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy.