Cd36, a class B scavenger receptor, functions as a monomer to bind acetylated and oxidized low-density lipoproteins

Cd36 is a small-molecular-weight integral membrane protein expressed in a diverse, but select, range of cell types. It has an equally diverse range of ligands and physiological functions, which has implicated Cd36 in a number of diseases including insulin resistance, diabetes, and, most notably, atherosclerosis. The protein is reported to reside in detergent-resistant microdomains within the plasma membrane and to form homo- and hetero-intermolecular interactions. These data suggest that this class B scavenger receptor may gain functionality for ligand binding, and/or ligand internalization, by formation of protein complexes at the cell surface. Here, we have overexpressed Cd36 in insect cells, purified the recombinant protein to homogeneity, and analyzed its stability and solubility in a variety of nonionic and zwitterionic detergents. Octylglucoside conferred the greatest degree of stability, and by analytical ultracentrifugation we show that the protein is monomeric. A solid-phase ligand-binding assay demonstrated that the purified monomeric protein retains high affinity for acetylated and oxidized low-density lipoproteins. Therefore, no accessory proteins are required for interaction with ligand, and binding is a property of the monomeric fold of the protein. Thus, the highly purified and functional Cd36 should be suitable for crystallization in octylglucoside, and the in vitro ligand-binding assay represents a promising screen for identification of bioactive molecules targeting atherogenesis at the level of ligand binding.     

Mitochondrial ribosomal protein S36 delays cell cycle progression in association with p53 modification and p21(WAF1/CIP1) expression

Ribosomal biogenesis is correlated with cell cycle, cell proliferation, cell growth and tumorigenesis. Some oncogenes and tumor suppressors are involved in regulating the formation of mature ribosome and affecting the ribosomal biogenesis. In previous studies, the mitochondrial ribosomal protein L41 was reported to be involved in cell proliferation regulating through p21(WAF1/CIP1) and p53 pathway. In this report, we have identified a mitochondrial ribosomal protein S36 (mMRPS36), which is localized in the mitochondria, and demonstrated that overexpression of mMRPS36 in cells retards the cell proliferation and delays cell cycle progression. In addition, the mMRPS36 overexpression induces p21(WAF1/CIP1) expression, and regulates the expression and phosphorylation of p53. Our result also indicate that overexpression of mMRPS36 affects the mitochondrial function. These results suggest that mMRPS36 plays an important role in mitochondrial ribosomal biogenesis, which may cause nucleolar stress, thereby leading to cell cycle delay.     

Insight into the mechanism of lipids binding and uptake by CD36 receptor

The membrane protein CD36 is a member of the class B scavenger receptor family. It plays a crucial role in some cardiovascular pathologies and metabolic diseases. Studying the mechanism of action of CD36 receptor is limited due to the absence of its tridimensional crystallized structure. The molecular docking method has allowed us to perform various simulation of the CD36 receptor interaction with their ligands involved in the development of some diseases. In this work, we predicted a tridimensional structure model of CD36 extracellular domain. In addition, we have achieved several tests of rigid and flexible docking by acting on residues proposed in previous experimental researches as essential in fixing of LFCAs. Furthermore, we have acted on regions that appear a key binding site of LFCAs. The physicoc hemical evaluation indicated the reliability of the proposed CD36 structure used for different molecular docking tests. Based on the docking outcome, we were able to propose the different steps of the mechanism allowing the interaction of fatty acids on CD36 receptor and their penetration into the cell cytoplasm. The obtained results and taking in consideration CD36 receptor as a therapeutic target will help us to suggest the mechanism by which an antagonist may inhibit this receptor by acting on its extracellular domain.     

Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress

Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and initiating tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB₁ and CB₂ G-protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development. This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.     

Relationship of number of remaining teeth to health-related quality of life in community-dwelling elderly

Objective: The aim of this study was to evaluate the relationship between number of remaining teeth and health‐related quality of life in community‐dwelling elderly. Subjects: A total of 207 participants who were community‐dwelling, 85 years of age. Data were from a population‐based study of age‐related general and oral health in Fukuoka Prefecture, Japan. Measurements: The Japanese version of the Short Form 36 Health Survey (SF‐36). Results: The mental component score for the participants, from the SF‐36, was higher than the Japanese national norm for those aged ≥70 years. There were no significant differences in the mean of any scores on the SF‐36 by having spouse, living with family, or education level. The mean of the SF‐36 scores of physical functioning (PF) and of the physical component scores were significantly higher in the 85‐year‐old participants with ≥20 teeth than in those with ≤19 teeth (p < 0.05 and p < 0.01 respectively). In addition, a significant difference (p < 0.05) was observed between the mean of participants with ≥20 teeth and those with ≤19 teeth after adjustment for region where the participant lived, activities of daily living (ADL), and sex. The PF (p < 0.001), role‐physical (p < 0.005), bodily pain (p < 0.001), vitality (p < 0.001), social functioning (p < 0.05), and physical component (p < 0.001) scores were significantly higher in participants with a good activities of daily living (ADL) assessment. However, ADL was not associated with the number of teeth. Conclusions: The findings of the present study indicated that 85‐year‐old participants with ≥20 teeth had better subjective physical health than those with ≤19 teeth.     

Cloning and expression of the gene encoding <Emphasis Type="BoldItalic">Streptomyces coelicolor</Emphasis> A3(2) α-galactosidase belonging to family 36

The α-galactosidase gene of Streptomyces coelicolor A3(2) was cloned, expressed in Escherichia coli and characterized. It consisted of 1497 nucleotides encoding a protein of 499 amino acids with a predicted molecular weight of 57,385. The observed homology between the deduced amino acid sequences of the enzyme and α-galactosidase from Thermus thermophilus was over 40%. The α-galactosidase gene was assigned to family 36 of the glycosyl hydrolases. The enzyme purified from recombinant E. coli showed optimal activity at 40 °C and pH 7. The enzyme hydrolyzed p-nitrophenyl-α-D-galactopyroside, raffinose, stachyose but not melibiose and galactomanno-oligosaccharides, indicating that this enzyme recognizes not only the galactose moiety but also other substrates.