Tumor necrosis factor alpha-induced glucose transporter (GLUT-1) mRNA stabilization in 3T3-L1 preadipocytes. Regulation by the adenosine-uridine binding factor.
ABSTRACT Tumor necrosis factor alpha (TNF alpha), 12-O-tetradecanoylphorbol-13-acetate and cAMP stimulate hexose transport in quiescent 3T3-L1 preadipocytes by stabilizing the relatively labile mRNA coding for the basal glucose transporter, GLUT-1. The 3'-UTR of GLUT-1 mRNA contains a single copy of the destabilizing AUUUA motif in the context of an AU-rich region. The adenosine-uridine binding factor (AUBF) is a cytosolic protein which interacts with similar AU-rich regions in a variety of labile cytokine and oncogene mRNAs. Here, we demonstrate that AUBF complexes in vitro with GLUT-1 mRNA through the AU-rich portion of the 3'-UTR. AUBF activity is very low in quiescent preadipocytes, but can be up-regulated by agonists such as TPA, TNF alpha, cAMP, and okadaic acid, all of which stabilize GLUT-1 mRNA. The time courses of TNF alpha- and TPA-mediated AUBF up-regulation and GLUT-1 mRNA stabilization are coincident, suggesting a cause and effect relationship.
SourceAvailable from: Alan R Prossin[Show abstract] [Hide abstract]
ABSTRACT: : Strong associations exist between tumor necrosis factor-α (TNF-α) and metabolic syndrome (MetS). Although TNF-α is associated with bipolar depression (BD), its role in atypical antipsychotic (AAP)-associated MetS in BD is unclear. Here, we investigate the potential intervening role of TNF-α in the indirect relationship between AAP treatment and MetS in BD. : Using a cross-sectional design, 99 euthymic BD volunteers were stratified by the presence or the absence of MetS (National Cholesterol Education Program Adult Treatment Panel III). Serum TNF-α concentration, determined via chemiluminescent immunometric assays, was compared between groups (ie, MetS or no MetS). We investigated the intervening effect of TNF-α on the relation between AAP treatment and MetS in BD using regression techniques. : Treatment with those antipsychotics believed associated with a higher risk for MetS (ie, AAPs: olanzapine, quetiapine, risperidone, paliperidone, clozapine) was found to be associated with significantly greater TNF-α (F1,88 = 11.2, P = 0.001, mean difference of 1.7 ± 0.51) and a higher likelihood of MetS (F1,88 = 4.5, P = 0.036) than in those not receiving treatment with an AAP. Additionally, TNF-α was greater (trending toward significance; T52 = 2.0, P = 0.05) in BD volunteers with MetS and was found to have a statistically significant effect on the indirect relationship between AAP treatment and elevated waist circumference in these BD volunteers. : These results identify TNF-α as a potential intervening variable of AAP-associated MetS in BD, not previously identified in this population. Future prospective studies could assess the predictive potential of TNF-α in determining risk of AAP-associated MetS in BD. Given previous evidence relating TNF-α and mood state in BD, this study increases the importance in understanding the role of TNF-α in "mind-body" interactions and renews discussions of the utility of research into the clinical efficacy of TNF-α antagonist treatment in mood disorders.Therapeutic drug monitoring 04/2013; 35(2):194-202. DOI:10.1097/FTD.0b013e31827e18d2 · 1.93 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Glucose serves as the major energy substrate and the main precursor for the synthesis of glycosaminoglycans in chondrocytes. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. This study examines molecular regulation of facilitated glucose transport in normal human articular chondrocytes by proinflammatory cytokines. IL-1β and TNF-α, and to a lesser degree IL-6, accelerate facilitated glucose transport as measured by [3H]2-deoxyglucose uptake. IL-1β induces an increased expression of glucose transporter (GLUT) 1 mRNA and protein, and GLUT9 mRNA. GLUT3 and GLUT8 mRNA are constitutively expressed in chondrocytes and are not regulated by IL-1β. GLUT2 and GLUT4 mRNA are not detected in chondrocytes. IL-1β stimulates GLUT1 protein glycosylation and plasma membrane incorporation. IL-1β regulation of glucose transport in chondrocytes depends on protein kinase C and p38 signal transduction pathways, and does not require phosphoinositide 3-kinase, extracellular signal-related kinase, or c-Jun N-terminal kinase activation. IL-1β-accelerated glucose transport in chondrocytes is not mediated by endogenous NO or eicosanoids. These results demonstrate that stimulation of glucose transport represents a component of the chondrocyte response to IL-1β. Two classes of GLUTs are identified in chondrocytes, constitutively expressed GLUT3 and GLUT8, and the inducible GLUT1 and GLUT9.The Journal of Immunology 12/2001; 167(12). DOI:10.4049/jimmunol.167.12.7001 · 5.36 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Interleukin-1β (IL-1β) is a potent cytokine that stimulates interstitial collagenase-1 (matrix metalloproteinase-1; MMP-1). In this study, we compared the mechanism(s) by which IL-1β induces collagenase gene expression in two very different cells, normal human foreskin fibroblasts (HFFs) and an aggressive breast cancer cell line, BC-8701 cells. Northern analysis showed that the time course of collagenase induction was distinct in the two cells: although both cells expressed low levels of MMP-1 constitutively, addition of IL-1β increased MMP-1 mRNA in HFFs by 1 h and levels remained high over a 24-h period. In contrast, MMP-1 levels in IL-1β-treated BC-8701 cells did not increase until 4 h, peaked by 12 h and then declined. To analyze the transcriptional response, we cloned and sequenced more than 4,300 bp of the human MMP-1 promoter, and from this promoter clone, we prepared a series of 5′-deletion constructs linked to the luciferase reporter and transiently transfected these constructs into both cell types to measure both basal and IL-1β induced transcription. When both cell types were uninduced, promoter fragments containing less than 2,900 bp gave only a minimal transcriptional response, while larger fragments showed increased transcriptional activity. With IL-1β treatment, significant responsiveness (P < 0.001) in HFFs was seen only with the larger fragments, while in the BC-8701 cells, all fragments were significantly induced with IL-1β. Finally, we found that IL-1β stabilized MMP-1 mRNA in normal fibroblasts, but not in BC-8701 breast cancer cells. We conclude that both the transcriptional and post-transcriptional regulation of MMP-1 gene expression by IL-1β is controlled by cell-type specific mechanisms, and we suggest that IL-1 induced MMP-1 expression in tumor cells and in neighboring stromal cells may amplify the invasive ability of tumor cells. J. Cell. Biochem. 66:322–336, 1977. © 1997 Wiley-Liss, Inc.Journal of Cellular Biochemistry 09/1997; 66(3):322 - 336. DOI:10.1002/(SICI)1097-4644(19970901)66:3<322::AID-JCB5>3.0.CO;2-R · 3.37 Impact Factor