1. Inflammation and ER stress differentially regulate STAMP2 expression and localization in adipocytes.
- Author
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Sikkeland, Jørgen, Lindstad, Torstein, Nenseth, Hatice Zeynep, Dezitter, Xavier, Qu, Su, Muhumed, Ridhwan M., Ertunc, Meric Erikci, Gregor, Margaret F., and Saatcioglu, Fahri
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INFLAMMATION ,ENDOPLASMIC reticulum ,GENE expression ,FAT cells ,PROTEIN transport - Abstract
Abstract Background Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress. Methods 3T3-L1 and MEF adipocytes were treated with ER stress inducers thapsigargin and tunicamycin, and inflammation inducer TNFα. The treatments effect on STAMP2 expression and enzymatic function was assessed. In addition, 3T3-L1 adipocytes and HEK cells were utilized for Stamp 2 promoter activity investigation performed with luciferase and ChIP assays. Results ER stress significantly reduced both STAMP2 mRNA and protein expression in cultured adipocytes whereas TNFα had the opposite effect. Concomitant with loss of STAMP2 expression during ER stress, intracellular localization of STAMP2 was altered and total iron reductase activity was reduced. Stamp 2 promoter analysis by reporter assays and chromatin immunoprecipitation, showed that induction of ER stress disrupts C/EBPα-mediated STAMP2 expression. Conclusion These data suggest a clear link between ER stress and quantitative and functional STAMP2-deficiency. Highlights • STAMP2 is of importance in the understanding of metabolic disease. • ER stress affects STAMP2 expression, distribution, and function in adipocytes. • Loss of C/EBPα binding to Stamp 2 promoter under ER stress decrease STAMP2 levels. • This implicates STAMP2 as a link between ER dysfunction and metabolic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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