Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy

Effects of NaCl and Na2SO4 salinity on plant growth, ion content and photosynthetic activity in Ocimum basilicum L.

Basil (Ocimum basilicum L., cultivar Genovese) plants were grown in Hoagland solution with or without 50 mM NaCl or 25 mM Na 2SO 4. After 15 days of treatment, Na 2SO 4 slowed growth of plants as indicated by root, stem and leaf dry weight, root length, shoot height and leaf area, and the effects were major of those induced by NaCl. Photosynthetic response was decreased more by chloride salinity than by sulphate. No effects in both treatments on leaf chlorophyll content, maximal efficiency of PSII photochemistry (F v/F m) and electron transport rate (ETR) were recorded. Therefore, an excess of energy following the limitation to CO 2 photoassimilation and a down regulation of PSII photochemistry was monitored under NaCl, which displays mechanisms that play a role in avoiding PSII photodamage able to dissipate this excess energy. Ionic composition (Na +, K +, Ca 2+, and Mg 2+) was affected to the same extent under both types of salinity, thus together with an increase in leaves Cl -, and roots SO 4 2- in NaCl and Na 2SO 4-treated plants, respectively, may have resulted in the observed growth retardation (for Na 2SO 4 treatment) and photosynthesis activity inhibition (for NaCl treatment), suggesting that those effects seem to have been due to the anionic component of the salts

Glycolytic control of adjuvant-induced macrophage survival: Role of PI3K, MEK1/2, and Bcl-2

Uptake by macrophages forms an important part of the mode of action of particulate adjuvants such as oil-in-water emulsions and alum. We have found previously that such adjuvants promote macrophage survival and suggested that this response may contribute to their efficacy. To explore this adjuvant activity further, we have investigated whether oil-in-water emulsion stimulates glucose uptake in macrophages and whether such uptake is relevant to the promotion of survival. We found that oil-in-water emulsion stimulated glucose uptake in a biphasic manner. The first acute phase was independent of mRNA and protein synthesis but appeared to require PI3K activity. In contrast, the second chronic phase was dependent on mRNA and protein synthesis. Importantly, the second phase of glucose uptake required MEK1/2 as well as PI3K activity, indicating that the MEK1/2 pathway can also contribute to cellular glucose uptake. The increased glucose transporter 1 expression during the second phase and long-term survival also appeared to be dependent on PI3K and MEK1/2 signaling pathways. Metabolism of the glucose was required for the emulsion-stimulated survival as well as the increase of prosurvival Bcl-2 transcript levels and maintenance of Bcl-2 protein expression. As transgenic overexpression of Bcl-2 enhances the survival of macrophages in the absence of growth factor, the glycolytic control of Bcl-2 levels may play a central role in emulsionstimulated macrophage survival. Enhanced glucose uptake by macrophages may therefore be critical to the action of particulate adjuvants. © Society for Leukocyte Biology