Impaired coactivator activity of the Gly482 variant of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) on mitochondrial transcription factor A (Tfam) promoter

Biochemical and Biophysical Research Communications
Yon-Sik ChoiYoungmi Kim Pak

Abstract

Mitochondrial dysfunction may cause diabetes or insulin resistance. Peroxisome proliferation-activated receptor-gamma (PPAR-gamma) coactivator-1 alpha (PGC-1alpha) increases mitochondrial transcription factor A (Tfam) resulting in mitochondrial DNA content increase. An association between a single nucleotide polymorphism (SNP), G1444A(Gly482Ser), of PGC-1alpha coding region and insulin resistance has been reported in some ethnic groups. In this study, we investigated whether a change of glycine to serine at codon 482 of PGC-1alpha affected the Tfam promoter activity. The cDNA of PGC-1alpha variant bearing either glycine or serine at 482 codon was transfected into Chang human hepatocyte cells. The PGC-1alpha protein bearing glycine had impaired coactivator activity on Tfam promoter-mediated luciferase. We analyzed the PGC-1alpha genotype G1444A and mitochondrial DNA (mtDNA) copy number from 229 Korean leukocyte genomic DNAs. Subjects with Gly/Gly had a 20% lower amount of peripheral blood mtDNA than did subjects with Gly/Ser and Ser/Ser (p<0.05). No correlation was observed between diabetic parameters and PGC-1alpha genotypes in Koreans. These results suggest that PGC-1alpha variants with Gly/Gly at 482nd amino acid may impair t...Continue Reading

References

Jan 12, 2000·Experimental & Molecular Medicine·C Y Han, Y K Pak
May 17, 2003·Science·Kitt Falk PetersenGerald I Shulman
Jul 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mary Elizabeth PattiLawrence J Mandarino
Jan 13, 2004·Biochemical and Biophysical Research Communications·Yon Sik ChoiYoungmi Kim Pak

❮ Previous
Next ❯

Citations

Mar 1, 2007·European Journal of Human Genetics : EJHG·Sean MylesMark Stoneking
Nov 30, 2011·Journal of Sports Sciences·Agnieszka MaciejewskaIldus I Ahmetov
May 21, 2011·BMC Medical Genetics·Joanne ClarkDavid K Simon
Mar 10, 2015·Internal Medicine·Yuichiro NishidaKeitaro Tanaka
Apr 21, 2016·The Journal of Endocrinology·Haijiang WuHuijun Duan
May 31, 2014·Biochemical and Biophysical Research Communications·Eun Jin LeeYoungmi Kim Pak
Dec 1, 2017·Endocrinology·Roxanne VandenbeekJennifer L Estall
Mar 15, 2012·Journal of Nutrigenetics and Nutrigenomics·Annie Bouchard-MercierMarie-Claude Vohl
Jun 8, 2018·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Negar ZamaninourSeyed Ali Keshavarz
Sep 13, 2018·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Ghaleb A OriquatMaher A Kamel
Sep 7, 2020·Mechanisms of Ageing and Development·Ioanna Daskalaki, Nektarios Tavernarakis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.