Troglitazone selectively inhibits glyoxalase I gene expression.
TLDR
This study shows that troglitazone is a selective inhibitor of the glyoxalase system, which could contribute to trog litazone's hepatotoxic action which has previously been reported in a small percentage of individuals.Abstract:
Aims/hypothesis:
The hyperglycaemia associated with diabetes causes excessive production of cytotoxic methylglyoxal, an α-oxo-aldehyde. The glyoxalase system, composed of glyoxalase I and glyoxalase II, with glutathione (GSH) as the cofactor, plays an important role in the detoxification of α-oxo-aldehydes. We tested the hypothesis that troglitazone, an insulin-sensitizing drug previously used in the treatment of Type II (non-insulin-dependent) diabetes mellitus, up-regulates the glyoxalase system either by increasing phase 2 enzyme activities and thereby increasing cellular GSH, or, by inducing glyoxalase enzyme activities.read more
Citations
More filters
Journal ArticleDOI
Methylglyoxal, the dark side of glycolysis
TL;DR: A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.
Journal ArticleDOI
Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence.
Michaela Diamant,Robert J. Heine +1 more
TL;DR: These agents were shown to decrease blood pressure, enhance myocardial function and fibrinolysis, as well as possess anti-inflammatory and other beneficial vascular effects, and seem to have differential effects on dyslipidaemia in patients with type 2 diabetes.
Journal ArticleDOI
Increased Methylglyoxal and Oxidative Stress in Hypertensive Rat Vascular Smooth Muscle Cells
TL;DR: This study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methyl glyoxal increases oxidative stress, activates NF-&kgr;B, and enhances ICAM-1 expression.
Journal ArticleDOI
Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells.
TL;DR: In conclusion, MG induces significant generation of NO and O2*- in rat VSMCs, which in turn causes ONOO- formation and the consequential ROS/RNS generation would alter cellular signaling pathways, contributing to the development of different insulin resistance states such as diabetes or hypertension.
Journal ArticleDOI
Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection
Mireille Bélanger,Jiangyan Yang,Jean-Marie Petit,Thierry Laroche,Pierre J. Magistretti,Igor Allaman +5 more
TL;DR: The presence of a highly efficient glyoxalase system in astrocytes was associated with lower accumulation of AGEs compared with neurons, a sixfold greater resistance to MG toxicity, and the capacity to protect neurons against MG in a coculture system.