HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 48, 38012-38021, December 1, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/48/38012    most recent M004078200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gong, Q. Articles by MacDonald, M. J. Search for Related Content PubMed PubMed Citation Articles by Gong, Q. Articles by MacDonald, M. J. Social Bookmarking                      What's this?

Functional Analysis of Two Promoters for the Human Mitochondrial Glycerol Phosphate Dehydrogenase Gene^*

Qiuming Gong, Laura J. Brown, and Michael J. MacDonald

From the Children's Diabetes Center, University of Wisconsin, Madison, Wisconsin 53706

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is abundant in the normal pancreatic insulin cell, but its level is lowered 50% by diabetes. To evaluate mGPD expression, we cloned and characterized the 5'-flanking region of the human mGPD gene. The gene has two alternative first exons and two promoters. 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- 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 of high 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 cells by 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 cell mGPD levels in diabetes.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) 350772.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. E. Silva Thermogenic Mechanisms and Their Hormonal Regulation Physiol Rev, April 1, 2006; 86(2): 435 - 464. [Abstract] [Full Text] [PDF]

				M. Rajkovic, R. Middendorff, M. G. Wetzel, D. Frkovic, S. Damerow, H. J. Seitz, and J. M. Weitzel Germ Cell Nuclear Factor Relieves cAMP-response Element Modulator {tau}-mediated Activation of the Testis-specific Promoter of Human Mitochondrial Glycerol-3-phosphate Dehydrogenase J. Biol. Chem., December 10, 2004; 279(50): 52493 - 52499. [Abstract] [Full Text] [PDF]

				J. M. Weitzel, N. B. Shiryaeva, R. Middendorff, M. Balvers, C. Radtke, R. Ivell, and H. J. Seitz Testis-Specific Expression of Rat Mitochondrial Glycerol-3-Phosphate Dehydrogenase in Haploid Male Germ Cells Biol Reprod, February 1, 2003; 68(2): 699 - 707. [Abstract] [Full Text] [PDF]

				A. Kirmizis, S. M. Bartley, and P. J. Farnham Identification of the Polycomb Group Protein SU(Z)12 as a Potential Molecular Target for Human Cancer Therapy Mol. Cancer Ther., January 1, 2003; 2(1): 113 - 121. [Abstract] [Full Text] [PDF]

				C. Tan, B. E. Tuch, J. Tu, and S. A. Brown Role of NADH Shuttles in Glucose-Induced Insulin Secretion From Fetal {beta}-Cells Diabetes, October 1, 2002; 51(10): 2989 - 2996. [Abstract] [Full Text] [PDF]