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Miox in Obesity Molecular Bases of Disease
This study highlights mechanisms concerning the pathobiology of tubular injury in the context of myo-inositol oxygenase (Miox), a tubular enzyme. The kidneys of mice fed a high fat diet (HFD) had increased Miox expression and activity, and the latter was related to phosphorylation of serine/threonine residues. Also, expression of sterol regulatory element-binding protein1 (Srebp1) and markers of cellular/nuclear damage was increased along with accentuated apoptosis and loss of tubular brush border. Similar results were observed in cells treated with palmitate/BSA. Multiple sterol-response elements and E-box motifs were fou...
Source: Journal of Biological Chemistry - January 15, 2016 Category: Chemistry Authors: Tominaga, T., Dutta, R. K., Joladarashi, D., Doi, T., Reddy, J. K., Kanwar, Y. S. Tags: Metabolism Source Type: research

Atf3/Pdx-1/Hdac1 Axis Prompts Metabolic Syndrome Gene Regulation
Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the p...
Source: Journal of Biological Chemistry - September 25, 2014 Category: Chemistry Authors: Kim, J. Y., Hwang, J.-Y., Lee, D. Y., Song, E. H., Park, K. J., Kim, G. H., Jeong, E. A., Lee, Y. J., Go, M. J., Kim, D. J., Lee, S. S., Kim, B.-J., Song, J., Roh, G. S., Gao, B., Kim, W.-H. Tags: Molecular Bases of Disease Source Type: research

Insulin, NF-{kappa}B, and Myocardin Signaling in Cardiac Myoblasts Signal Transduction
Hyperinsulinemia contributes to cardiac hypertrophy and heart failure in patients with the metabolic syndrome and type 2 diabetes. Here, high circulating levels of tumor necrosis factor (TNF)-α may synergize with insulin in signaling inflammation and cardiac hypertrophy. We tested whether high insulin affects activation of TNF-α-induced NF-κB and myocardin/serum response factor (SRF) to convey hypertrophy signaling in cardiac myoblasts. In canine cardiac myoblasts, treatment with high insulin (10−8 to 10−7 m) for 0–24 h increased insulin receptor substrate (IRS)-1 phosphorylation at Ser-307, decreased protein leve...
Source: Journal of Biological Chemistry - July 10, 2014 Category: Chemistry Authors: Madonna, R., Geng, Y.-J., Bolli, R., Rokosh, G., Ferdinandy, P., Patterson, C., De Caterina, R. Tags: Gene Regulation Source Type: research

KLF14 and SK1 Lipid Signaling DNA and Chromosomes
In this study, we identified SK1 as a target of the canonical FGF2/FGF receptor 1 activation pathway in endothelial cells and sought to identify novel transcriptional pathways that mediate lipid signaling. Studies using the 1.9-kb SK1 promoter and deletion mutants revealed that basal and FGF2-stimulated promoter activity occurred through two GC-rich regions located within 633 bp of the transcription start site. Screening for GC-rich binding transcription factors that could activate this site demonstrated that KLF14, a gene implicated in obesity and the metabolic syndrome, binds to this region. Congruently, overexpression o...
Source: Journal of Biological Chemistry - May 30, 2014 Category: Chemistry Authors: de Assuncao, T. M., Lomberk, G., Cao, S., Yaqoob, U., Mathison, A., Simonetto, D. A., Huebert, R. C., Urrutia, R. A., Shah, V. H. Tags: Gene Regulation Source Type: research