Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter

Kajihara, Miwako; Sone, Hirohito; Amemiya, Michiyo; Katoh, Yohei; Isogai, Masashi; Shimano, Hitoshi; Yamada, Nobuhiro; Takahashi, Satoru

doi:10.1016/j.bbrc.2003.10.196

Cited by 60 publications

(61 citation statements)

References 50 publications

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“…Mutation of the PDX-1 (A3) (29) and MafA (A2) (22) sites of the preproinsulin promoter (30) blocked the activation by either glucose or coinjected PASK, whereas mutation of NeuroD1͞Beta2 (E1)-binding site had much smaller effects (Fig. 3C).…”

Section: Resultsmentioning

confidence: 96%

“…MIN6 ␤ cells (27) (passages [19][20][21][22][23][24][25][26][27][28][29][30] were grown in DMEM containing 15% FCS, 25 mM glucose, 5.4 mM KCl, 2 mM glutamine, 100 mM 2-mercaptoethanol, 100 units͞ml Ϫ1 penicillin, and 100 g͞ml Ϫ1 streptomycin in a humidified atmosphere at 37°C with 5% CO 2 , and seeded onto poly(L)-lysinecoated coverslips for microinjection. Cells were transfected with Lipofectamine 2000 or TransIT-TKO (for siRNA).…”

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confidence: 99%

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Involvement of Per–Arnt–Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose

Xavier

Rutter

2004

Proc. Natl. Acad. Sci. U.S.A.

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Per-Arnt-Sim (PAS) domain-containing kinases are common in prokaryotes, but a mammalian counterpart has only recently been described. Although the PAS domain of the mammalian PAS kinase (PASK) is closely related to the bacterial oxygen sensor FixL, it is unclear whether PASK activity is changed in mammalian cells in response to nutrients and might therefore contribute to signal transduction by these or other stimuli. Here, we show that elevated glucose concentrations rapidly increase PASK activity in pancreatic islet ␤ cells, an event followed by the accumulation of both PASK mRNA and protein. Demonstrating a physiological role for PASK activation, comicroinjection into clonal ␤ cells of cDNA encoding wild-type PASK, or PASK protein itself, mimics the induction of preproinsulin promoter activity by high glucose concentrations. Conversely, anti-PASK antibodies block promoter activation by the sugar, and the silencing of PASK expression by RNA interference suppresses the up-regulation by glucose of preproinsulin and pancreatic duodenum homeobox 1 gene expression, without affecting glucose-induced changes in the levels of mRNAs encoding glucokinase or uncoupling protein 2. We conclude that PASK is an important metabolic sensor in nutrient-sensitive mammalian cells and plays an unexpected role in the regulation of key genes involved in maintaining the differentiated phenotype of pancreatic ␤ cells.

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Section: Resultsmentioning

confidence: 96%

mentioning

confidence: 99%

Involvement of Per–Arnt–Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose

Xavier

Rutter

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…A series of AIM promoter-luciferase constructs were co-transfected with a MafB expression vector 48 into the human lung adenocarcinoma epithelial cell line H441. The Mafb promoter-luciferase constructs were co-transfected with LXRa and RXRa expression vectors into RAW264.7 cells.…”

Section: Methodsmentioning

confidence: 99%

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

et al. 2014

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“…Furthermore, MafA has been found to be required for the formation and development of mature islet beta cells (20). Regulation of the insulin gene by MafA (11,12,20,22) occurs via binding to the RIPE-3b1/C1 element of the insulin promoter, which is similar to the binding sequence referred to as Maf-recognition element(MARE). Loss of this essential activator of insulin gene transcription greatly compromises insulin gene expression.…”

Section: Western and Northern Analyses Formentioning

confidence: 99%

Oxidative Stress-mediated, Post-translational Loss of MafA Protein as a Contributing Mechanism to Loss of Insulin Gene Expression in Glucotoxic Beta Cells

Harmon

Stein

Robertson

2005

Journal of Biological Chemistry

213

166

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After the onset of type 2 diabetes, chronic hyperglycemia causes glucotoxic changes in many tissues (1, 2). Glucose toxicity in the pancreatic islet beta cell secondarily leads to further defects in beta cell function, including decreases in insulin reporter activity, gene expression, content, and secretion (3). Antioxidants have been shown to prevent these adverse changes in experimental models (4, 5). We previously observed that loss of insulin gene expression is accompanied by decreased binding to the promoter region of two important transcription factors, PDX-1 1 (STF-1, IDX-1, IPF-1) and RIPE-3b1 activator (6 -8). PDX-1 is required for pancreatic development and is a key regulator of insulin gene expression. Mutations within the RIPE-3b1/C1 element of the insulin promoter markedly reduce glucose-responsive insulin gene expression (7). We also reported that loss of RIPE-3b1 binding precedes the loss of PDX-1 binding to the insulin promoter as glucotoxicity develops (8). The chronology of these losses is likely to be important in light of a recent report that RIPE-3b1/MafA directly activates PDX-1 transcription (9).The work in this study features the use of HIT-T15 cells, a glucose-responsive beta cell line that has proven over the past decade to reproduce the molecular changes in gene expression that are caused by glucose toxicity in vivo in animal models. Since isolated islets cannot be chronically cultured to study the adverse effects of high glucose concentrations over many months, this cell line is a valuable surrogate. In our previous work, reconstitution of late passage glucotoxic HIT-T15 cells by transient transfection with PDX-1 partially restored insulin promoter activity (8). Since RIPE-3b1 had not yet been cloned, we were unable to extend our studies with this transcription factor but hypothesized that reconstitution of the cells with both PDX-1 and RIPE-3b1 activator would lead to greater recovery of insulin promoter activity. With the recent cloning and identification of RIPE-3b1 activator as MafA (10 -12), we have been able to perform new studies to examine 1) whether levels of MafA mRNA and protein are decreased in glucotoxic beta cells; 2) the mechanism of MafA protein degradation; 3) whether the antioxidant, N-acetylcysteine, can prevent glucotoxicity-induced loss of MafA protein and binding to the insulin promoter; and 4) whether overexpression of MafA and PDX-1 together can restore insulin promoter activity and mRNA levels more fully than PDX-1 alone. MATERIALS AND METHODSCell Culture-HIT-T15 cells were maintained in RPMI 1640 media containing 10% fetal bovine serum and 11.1 mM glucose as described previously (13). Cells were categorized as early passage (p71-75) or late passage (p123-128), with each passage occurring weekly. Chronic culturing of HIT-T15 cells with N-acetyl-L-cysteine (Sigma; 0.5, 1, or 5 mM) added to the media was begun at p70.

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Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter

Cited by 60 publications

References 50 publications

Involvement of Per–Arnt–Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose

Involvement of Per–Arnt–Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

Oxidative Stress-mediated, Post-translational Loss of MafA Protein as a Contributing Mechanism to Loss of Insulin Gene Expression in Glucotoxic Beta Cells

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