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Titolo:
Functional analysis of two promoters for the human mitochondrial glycerol phosphate dehydrogenase gene
Autore:
Gong, QM; Brown, LJ; MacDonald, MJ;
Indirizzi:
Univ Wisconsin, Childrens Diabet Ctr, Madison, WI 53706 USA Univ Wisconsin Madison WI USA 53706 ens Diabet Ctr, Madison, WI 53706 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 48, volume: 275, anno: 2000,
pagine: 38012 - 38021
SICI:
0021-9258(200012)275:48<38012:FAOTPF>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBUNIT-IV GENE; LINKED GLYCEROPHOSPHATE DEHYDROGENASE; BINDING-PROTEIN-ALPHA; PANCREATIC-ISLETS; GLYCEROL-3-PHOSPHATE DEHYDROGENASE; PYRUVATE-CARBOXYLASE; TRANSCRIPTION FACTOR; BETA-CELLS; MULTIPLE TRANSCRIPTS; 5'-END HETEROGENEITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: MacDonald, MJ Univ Wisconsin, Sch Med, Rm 3459,1300 Univ Ave, Madison, WI 53706 USA Univ Wisconsin Rm 3459,1300 Univ Ave Madison WI USA 53706 SA
Citazione:
Q.M. Gong et al., "Functional analysis of two promoters for the human mitochondrial glycerol phosphate dehydrogenase gene", J BIOL CHEM, 275(48), 2000, pp. 38012-38021

Abstract

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is abundant in the normal pancreatic insulin cell, but its level is lowered 50% by diabetes. Toevaluate mGPD expression, we cloned and characterized the 5'-flanking region of the human mGPD gene. The gene has two alternative first exons and twopromoters. The downstream promoter (B) is 10 times more active than the upstream promoter (A) in insulin secreting cells (INS-1) and HeLa cells. Promoter B has higher activity in INS-1 than in non-beta cells. Deletion and mutation analysis suggested that a NRF-2 binding site at -94 to -101 and an E2F binding site at -208 to -215 are important regulatory cis elements in promoter B, Gel mobility shift assays indicated that the -94 to -101 region binds the NRF-2 protein. When INS-1 cells were maintained in the presence ofhigh glucose (25 mM) for 7 days, mGPD was the only 1 of 6 enzyme activities lowered (53%), mGPD promoter B activity was reduced by 60% in INS-1 cellsby the high glucose, but in HepG2 cells and HeLa cells, promoter B activity was unchanged or slightly increased. Deletion analysis indicated the glucose responsiveness was distributed across the region from -340 to -260 in promoter B. The results indicate that mGPD gene transcription in the beta cell is regulated differently from other cells and that decreased mGPD promoter B transcription is at least in part the cause of the decreased beta cellmGPD levels in diabetes.

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Documento generato il 07/04/20 alle ore 23:18:16