Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated albumin

Publication date: January 2017
Source:Free Radical Biology and Medicine, Volume 102
Author(s): Jessica Patche, Dorothée Girard, Aurélie Catan, Florence Boyer, Anthony Dobi, Cynthia Planesse, Nicolas Diotel, Alexis Guerin-Dubourg, Pascal Baret, Susana B. Bravo, Beatriz Paradela-Dobarro, Ezequiel Álvarez, M. Faadiel Essop, Olivier Meilhac, Emmanuel Bourdon, Philippe Rondeau
Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively. Our data reveal increased oxidative stress biomarkers and lipid accumulation in plasma and livers of diabetic mice, together with albumin glycoxidation. Purified mouse albumin modifications resembled those typically found in diabetic patients, i.e. degree of glycation, carbonylation, AGE levels and in terms of chemical composition. Receptor for AGE expression and reactive oxygen species production were upregulated in db/db mouse livers, together with impaired proteolytic, antioxidant and mitochondrial respiratory activities. In parallel, acute exposure of HepG2 cells to glycated albumin also elicited intracellular free radical formation. Together this study demonstrates that AGE-modified albumin can trigger damaging effects on the liver, i.e. by increasing oxidative stress, attenuating antioxidant capacity, and by impairment of hepatic proteolytic and respiratory chain enzyme activities.

Graphical abstract

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