Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation

Journal of Clinical Biochemistry and Nutrition
Hiroyuki YasudaTetsuo Adachi

Abstract

Exendin-4 is an agonist of the glucagon-like peptide 1 receptor (GLP-1R) and is used in the treatment of type 2 diabetes. Since human GLP-1R has been identified in various cells besides pancreatic cells, exendin-4 is expected to exert extrapancreatic actions. It has also been suggested to affect gene expression through epigenetic regulation, such as DNA methylation and/or histone modifications. Furthermore, the expression of extracellular-superoxide dismutase (EC-SOD), a major SOD isozyme that is crucially involved in redox homeostasis, is regulated by epigenetic factors. In the present study, we demonstrated that exendin-4 induced the demethylation of DNA in A549 cells, which, in turn, affected the expression of EC-SOD. Our results showed that the treatment with exendin-4 up-regulated the expression of EC-SOD through GLP-1R and demethylated some methyl-CpG sites (methylated cytosine at 5'-CG-3') in the EC-SOD gene. Moreover, the treatment with exendin-4 inactivated DNA methyltransferases (DNMTs), but did not change their expression levels. In conclusion, the results of the present study demonstrated for the first time that exendin-4 regulated the expression of EC-SOD by reducing the activity of DNMTs and demethylation of DNA w...Continue Reading

References

Sep 1, 1994·The European Respiratory Journal·I VachierP Godard
Sep 9, 1998·The American Journal of Physiology·T OokawaraH Ohno
Sep 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·P Strålin, S L Marklund
Jul 30, 2003·Free Radical Biology & Medicine·Cheryl L FattmanTim D Oury
Apr 20, 2004·Current Topics in Developmental Biology·Taiping Chen, En Li
Oct 27, 2004·Diabetes Care·John B BuseUNKNOWN Exenatide-113 Clinical Study Group
Jan 18, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Donald D Heistad
Feb 24, 2006·International Journal of Clinical Practice·E WrightL C Glass
Jun 15, 2006·Antioxidants & Redox Signaling·Alison C CaveAjay M Shah
Mar 4, 2008·American Journal of Respiratory Cell and Molecular Biology·Igor N ZelkoRodney J Folz
Apr 21, 2009·FEBS Letters·Robert S Illingworth, Adrian P Bird
May 28, 2009·Journal of the American Society of Nephrology : JASN·Hiroki FujitaTakamune Takahashi
Oct 1, 2009·Nature Reviews. Genetics·Peter A Jones, Gangning Liang
Oct 20, 2009·European Journal of Pharmacology·Lasse Sommer KristensenLise Lotte Hansen
Mar 6, 2012·Biochimica Et Biophysica Acta·Raghunath Chatterjee, Charles Vinson
Apr 23, 2013·Free Radical Biology & Medicine·Tetsuro KamiyaTetsuo Adachi
Sep 11, 2013·International Review of Cell and Molecular Biology·K Naga Mohan, J Richard Chaillet
Feb 11, 2014·Free Radical Biology & Medicine·Zita A SibenallerJoseph J Cullen

❮ Previous
Next ❯

Citations

Aug 25, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Kunio YuiYohei Kawasaki
Dec 3, 2016·Biological & Pharmaceutical Bulletin·Shuhei HattoriTetsuo Adachi
Jan 7, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Linda SommeseClaudio Napoli
Oct 17, 2019·Postgraduate Medicine·Pavlina A Andreeva-GatevaIvanka I Dimova
Jun 7, 2017·Journal of Clinical Biochemistry and Nutrition·Shunpei MorisawaTetsuo Adachi
Nov 30, 2016·Journal of Clinical Biochemistry and Nutrition·Hiroyuki YasudaTetsuo Adachi
Sep 3, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tetsuro Kamiya
Oct 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lucia ScisciolaMichelangela Barbieri

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
PCR
protein assay
histone acetylation
acetylation

Software Mentioned

MethPrimer

Related Concepts

Related Feeds

Cardiovascular Biology of GLP-1

Glucagon-like peptide 1 (GLP-1) plays a role in glucose metabolism, energy homeostasis, and inflammation suppression. GLP-1 receptor signaling has been shown to impact cardiovascular function. This feed focuses on the role of GLP-1 and GLP-1 receptor agonists on cardiovascular biology.