SEAP activity serves for demonstrating ER stress induction by glucolipotoxicity as well as testing ER stress inhibitory potential of therapeutic agents

Molecular and Cellular Biochemistry
Raji LeninMuthuswamy Balasubramanyam

Abstract

Endoplasmic reticulum (ER) stress is emerging as a unifying paradigm and one of the underlying mechanisms in the genesis of diabetes and its complications. While this has prompted the development of ER stress inhibitors, there is a limitation in monitoring of ER stress in vitro and in vivo by reliable methodologies. We validated the secreted alkaline phosphatase (SEAP) activity as a surrogate marker of ER stress in mouse β-TC6 cells exposed to glucolipotoxicity or tunicamycin and studied insulin secretion along with alterations in ER stress markers. SEAP activity assay was measured using the Great EscAPe SEAP kit, insulin levels were determined by Mercodia reagents and mRNA expression of ER stress markers was quantified by real-time PCR. SEAP activity in β-cells was significantly decreased (indicating increased ER stress) on exposure either to glucolipotoxicity or tunicamycin. This was accompanied by an increased mRNA expression of ER stress markers (GRP-78, PERK, IRE1α, ATF6, XBP-1, and CHOP) and decreased insulin secretion. Treating the cells with phenylbutyric acid normalized SEAP activity, decreased mRNA expression of ER stress markers and improved insulin secretion. Interestingly, cells exposed to different classes of anti...Continue Reading

References

Jan 1, 1992·Methods in Enzymology·B R Cullen, M H Malim
Jun 1, 1994·Analytical Biochemistry·I BronsteinL J Kricka
Sep 23, 2000·American Journal of Physiology. Endocrinology and Metabolism·K MinamiS Seino
Jun 12, 2002·Molecular Biology of the Cell·Christof TaxisDieter H Wolf
Nov 12, 2003·Experimental Biology and Medicine·Eiichi ArakiMasataka Mori
Jan 2, 2004·Nature Medicine·Takao IwawakiMasayuki Miura
Oct 2, 2004·Nature Medicine·Changhui MaoAmy S Lee
Oct 16, 2004·Science·Umut OzcanGökhan S Hotamisligil
Feb 9, 2005·Molecular & Cellular Proteomics : MCP·Thomas SparreFlemming Pociot
Jun 15, 2006·The Journal of Toxicological Sciences·Morihiko HirotaSetsuya Aiba
Jan 25, 2008·The EMBO Journal·Tiziana Anelli, Roberto Sitia
Jan 29, 2008·Recent Patents on Cardiovascular Drug Discovery·Kaushik Desai, Lingyun Wu
Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kristin D JeffreyJames D Johnson
Jul 29, 2008·Molecular and Cellular Endocrinology·Tea Sundsten, Henrik Ortsäter
Jan 16, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ana RicobarazaAna García-Osta
Jan 21, 2011·Molecular and Cellular Biochemistry·M BalasubramanyamV Mohan
Jan 26, 2011·Annals of the New York Academy of Sciences·Tomasz Szkudelski, Katarzyna Szkudelska
Jun 27, 2012·The Journal of Cell Biology·Shiyu Wang, Randal J Kaufman
Nov 28, 2012·PloS One·Melanie GertzClemens Steegborn
Apr 19, 2013·Diabetes Care·Lisa R StaimezK M Venkat Narayan

❮ Previous
Next ❯

Citations

Sep 17, 2016·Medicinal Research Reviews·Paulo MatafomeRaquel Seiça
Aug 29, 2018·Environmental Toxicology·Hung-Sheng ShangJing-Gung Chung
Apr 27, 2021·Journal of Receptor and Signal Transduction Research·Mustafa Kırça, Akın Yeşilkaya

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Diabetes

This feed focuses on the latest research on biomarkers used for monitoring disease progression in diabetes.