3,4-DGE is cytotoxic and decreases HSP27/HSPB1 in podocytes

Archives of Toxicology
Maria D Sanchez-NiñoAlberto Ortiz

Abstract

Hyperglycemia is the key driver of diabetic complications and increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse biological effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was identified as the most toxic glucose degradation product in peritoneal dialysis fluids. In addition, 3,4-DGE is present in high-fructose corn syrup, and its precursor 3-deoxyglucosone is increased in diabetes. The role of 3,4-DGE in glomerular injury had not been addressed. We studied the effects of 3,4-DGE on cultured human podocytes and in vivo in mice. 3,4-DGE induced apoptosis in podocytes in a dose- and time-dependent manner. 3,4-DGE promoted the release of cytochrome c from mitochondria and activation of caspase-3. While high glucose concentrations increased the levels of the podocyte intracellular antiapoptotic protein HSP27/HSPB1, 3,4-DGE decreased the expression of podocyte HSP27/HSPB1. Apoptosis induced by 3,4-DGE was caspase-dependent and could be prevented by the broad-spectrum caspase inhibitor zVAD-fmk. Antagonism of Bax by a Ku-70-derived peptide also prevented apoptosis. Intravenous administration of 3,4-DGE...Continue Reading

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Citations

Nov 26, 2015·Archives of Toxicology·Christoph van Thriel
Nov 30, 2015·Archives of Toxicology·Ahmed Ghallab
Dec 2, 2015·Archives of Toxicology·Klaus Golka
Oct 7, 2015·Frontiers in Immunology·Lara Valiño-RivasMaria Dolores Sanchez-Niño
Nov 19, 2020·Journal of Clinical Medicine·Hernán TrimarchiMaria Dolores Sánchez-Niño

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