Activation of HIF by DMOG halted the progression of proteinuria and attenuated structural damage by preventing podocyte injury in the remnant kidney model. This renoprotection was accompanied by a reduction of oxidative stress, inflammation and fibrosis.

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Retinoic acid (RA) is one of the major components of vitamin A.In the present study, we found that retinoic acid activated AMPactivated protein kinase (AMPK). RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), whereas the inhibition of AMPK blocked RA-induced Rac1 activation. Moreover, cofilin, an actin polymerization regulator, was activated when incubated with RA. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPK ␣1 blocked RA-induced cofilin phosphorylation. Additionally, we found that retinoic acid-stimulated glucose uptake in differentiated C2C12 myoblast cells and activated p38 mitogen-activated protein kinase (MAPK). Finally, the inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake. In summary, our results suggest that retinoic acid may have cytoskeletal roles in skeletal muscle cells via stimulation of the AMPK-Rac1-PAK-cofillin pathway and may also have beneficial roles in glucose metabolism via stimulation of the AMPK-p38 MAPK pathway.Retinoids are important regulators of differentiation and cell proliferation. Induction of differentiation by retinoic acid has been observed in various cell systems, such as endothelial, neuronal, and lung cancers (1). Retinoic acid has been shown to inhibit the growth of breast cancer cells and to reduce the number of tumors in animal models (2, 3). The anti-tumor potential of retinoids has been demonstrated by their ability to inhibit the growth of several human cancers, including colon cancer, prostate cancer, and melanoma (4, 5). Retinoic acid mediates its effects by binding to its receptors, retinoid acid receptor, or retinoid X receptor, followed by heterodimerization of the receptors and their recognition of binding to retinoid acid receptor element-containing promoters.AMP-activated protein kinase (AMPK) 2 is a phylogenetically conserved intracellular energy sensor that plays a central role in the regulation of glucose and lipid metabolism. AMPK, a heterotrimeric complex comprised of a catalytic subunit and two regulatory subunits, is activated when cellular energy is depleted (6). Upon activation by allosteric binding of AMP or phosphorylation at Thr 172 of the catalytic subunit by AMPK kinase, AMPK accelerates ATP-generating catabolic pathways, including glucose and fatty acid oxidation (7-9) while simultaneously reducing ATP-consuming anabolic pathways including cholesterol, fatty acid, and triacylglycerol synthesis (10). In addition to its roles in energy homeostasis, AMPK also has been shown to regulate the endothelial nitric-oxide synthase pathway through Rac1 (11). The involvement of interaction of Rac1 with AMPK has been implicated in many of the biological effects of AMPK in cytoskeletal remodeling.Small GTPases of the Rho family have diverse effects on cellular structure and function. Depending on the cell type, specific Rho GTPases induce particular surface protrusions generated by actin-remodeling reactions t...

Streptococcus pneumoniae is a causative agent of high morbidity and mortality. Although sugar moieties have been recognized as ligands for initial contact with the host, only a few exoglycosidases have been reported to occur in S. pneumoniae. In this study, a putative ␤-galactosidase, encoded by the bgaC gene of S. pneumoniae, was characterized for its enzymatic activity and virulence. The recombinant BgaC protein, expressed and purified from Escherichia coli, was found to have a highly regiospecific and sugar-specific hydrolysis activity for the Gal␤1-3-GlcNAc moiety of oligosaccharides. Interestingly, the BgaC hydrolysis activity was localized at the cell surface of S. pneumoniae, indicating that BgaC is expressed as a surface protein although it does not have a typical signal sequence or membrane anchorage motif. The surface localization of BgaC was further supported by immunofluorescence microscopy analysis using an antibody raised against BgaC and by a reassociation assay with fluorescein isothiocyanate-labeled BgaC. Although the bgaC deletion mutation did not significantly attenuate the virulence of S. pneumoniae in vivo, the bgaC mutant strain showed relatively low numbers of viable cells compared to the wild type after 24 h of infection in vivo, whereas the mutant showed higher colonization levels at 6 and 24 h postinfection in vivo. Our data strongly indicate for the first time that S. pneumoniae bgaC encodes a surface ␤-galactosidase with high substrate specificity that is significantly associated with the infection activity of pneumococci.The human pathogen Streptococcus pneumoniae (the pneumococcus) is a gram-positive coccus and a member of the lactic acid bacterium group. S. pneumoniae is the major causative agent of lobar pneumonia, otitis media, and meningitis and is carried in the nasopharynx of healthy individuals, a major reservoir for pneumococcal infections (16). In the human host, S. pneumoniae encounters a variety of glycoconjugates, including host defense molecules, mucin, and binding sites exposed on the epithelial surface. Similar to other pathogenic microbes, S. pneumoniae produces both secreted and surface-associated glycosidases that may modify glycoconjugates in the host environment (2, 6, 41). Oligosaccharides are recognized as receptors for invasion or as dietary substrates for the maintenance of colonial microflora. Recent studies have shown that deglycosylation of human glycoconjugates by the sequential actions of exoglycosidases, including neuraminidase (NanA), ␤-galactosidase (BgaA), and N-acetylglucosaminidase (StrH), is essential for S. pneumoniae colonization and pathogenesis (19, 33). Furthermore, S. pneumoniae can utilize monosaccharides liberated from human glycoconjugates to sustain growth by sequential deglycosylation of host glycoconjugates through the activities of these exoglycosidases (NanA, BgaA, and StrH) and another neuraminidase (NanB) (5).The enzyme ␤-galactosidase, classified as EC 3.2.1.23, hydrolyzes the terminal nonreducing galactose from oligosaccharides. ...

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