SMIT1 mediates the production of reactive oxygen species induced by hyperglycemia in the heart
(2017)
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- Authors
- Supervisors
- Beauloye , Christophe
- Abstract
- Hyperglycemia (HG) is a powerful trigger of reactive oxygen species (ROS) production in the heart. In cardiomyocytes, HG stimulates ROS production through NADPH oxidase 2 (NOX2) activation. This NOX2 activation is independent of glucose metabolism but requires glucose detection by a sodium/glucose cotransporter (SGLT). Seven SGLT isoforms are known although their expression and function in the heart remain unknown. In this work, we showed that SGLT1 and SMIT1 are the two isoforms mainly expressed in the heart. Based on substrate specificity, we identified SMIT1 as the isoform that mediates ROS production in response to HG. Indeed, myo-inositol (transported through SMIT1) reproduced toxic effects of HG. SMIT1 overexpression sensitized cardiomyocytes to HG and exacerbated the resulting glucotoxicity, whereas its deletion prevented HG-induced NOX2 activation. Ionic changes, sodium/calcium exchanger and protein kinase C β were identified as key elements in the signaling pathway downstream of SMIT1. Finally, by activating AMP-activated protein kinase (AMPK), the glucagon-like peptide-1 (GLP-1) prevented HG-induced ROS production.
- Affiliations
Citations
Van Steenbergen, A. (2017). SMIT1 mediates the production of reactive oxygen species induced by hyperglycemia in the heart. https://hdl.handle.net/2078.5/92946