Loss of Egr-1 sensitizes pancreatic β-cells to palmitate-induced ER stress and apoptosis

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Mun-Wai CheongYau-Sheng Tsai

Abstract

Pancreatic β-cells are particularly susceptible to fatty-acid-induced endoplasmic reticulum (ER) stress and apoptosis. To understand how β-cells sense fatty acid stimuli and translate into a long-term adaptive response, we investigated whether palmitic acid (PA) regulates early growth response-1 (Egr-1), an immediate-early transcription factor, which is induced by many environmental stimuli and implicated in cell proliferation, differentiation, and apoptosis. We found that Egr-1 was rapidly and transiently induced by PA in MIN6 insulinoma cells, which was accompanied by calcium influx and ERK1/2 phosphorylation. Calcium chelation and MEK1/2 inhibition blocked PA-induced Egr-1 upregulation, suggesting that PA induces Egr-1 expression through a calcium influx-MEK1/2-ERK1/2 cascade. Knockdown of Egr-1 increased PA-induced caspase-3 activation and ER stress markers and decreased PA-induced Akt phosphorylation and insulin secretion and signaling. Akt replenishment and insulin supplementation rescued PA-induced apoptosis in Egr-1 knockdown cells. These results suggest that the absence of Egr-1 loses its ability to couple the short-term insulin/Akt pathway to long-term survival adaptation. Finally, Egr-1-deficient mouse islets are mor...Continue Reading

References

Apr 28, 1995·The Journal of Biological Chemistry·S L LeeJ Milbrandt
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M ShimabukuroR H Unger
Aug 1, 1998·The Journal of Biological Chemistry·M Pap, G M Cooper
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Jan 10, 2002·The Journal of Biological Chemistry·Marcela BrissovaAlvin C Powers
Oct 18, 2002·Journal of Cellular Physiology·Gerald Thiel, Giuseppe Cibelli
Oct 24, 2002·The Journal of Biological Chemistry·Christian E WredeChristopher J Rhodes
Nov 26, 2002·Nature·Jiro HirosumiGökhan S Hotamisligil
Apr 17, 2003·The Journal of Clinical Investigation·James D JohnsonKenneth S Polonsky
Nov 15, 2006·Molecular and Cellular Endocrinology·Susanne SchnellChristof Schöfl
Dec 1, 2007·Endocrine Reviews·Décio L EizirikMiriam Cnop
Jan 29, 2008·Current Diabetes Reviews·Hideaki KanetoYoshimitsu Yamasaki
Aug 27, 2009·Journal of Cell Science·Sabine I MayerGerald Thiel
Sep 1, 2009·Biochimica Et Biophysica Acta·Vincent PoitoutGhislaine Fontés
Oct 2, 2009·Future Oncology·Delphine Gitenay, Véronique T Baron
Nov 16, 2010·Cell Calcium·Michael F RitchieJonathan Soboloff
Dec 3, 2013·Canadian Journal of Physiology and Pharmacology·Luca PaciniAntonella Calogero

❮ Previous
Next ❯

Citations

Mar 11, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Li-Chun HoYau-Sheng Tsai
May 20, 2016·Intractable & Rare Diseases Research·Jing TianGuosheng Jiang
Dec 29, 2019·The Journal of Biological Chemistry·Joao Pedro Werneck-de-CastroErnesto Bernal-Mizrachi
Sep 28, 2020·Journal of Animal Physiology and Animal Nutrition·Tao ZhangXiao-Li Chu
May 26, 2021·Trends in Endocrinology and Metabolism : TEM·Matthew Wortham, Maike Sander

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.