Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells

Abstract

AimsHigh levels of glucose and reactive carbonyl intermediates of its degradation pathway such as methylglyoxal (MG) may contribute to diabetic complications partly via increased generation of reactive oxygen species (ROS). This study focused on glutathione peroxidase-1 (GPx1) expression and the impact of carbonylation as an oxidative protein modification on GPx1 abundance and activity in human umbilical vein endothelial cells (HUVEC) under conditions of mild to moderate oxidative stress.ResultsHigh extracellular glucose and MG enhanced intracellular ROS formation in HUVECs. Protein carbonylation was only transiently augmented pointing to an effective antioxidant defense in these cells. Nitric oxide synthase expression was decreased under hyperglycemic conditions but increased upon exposure to MG, whereas superoxide dismutase expression was not significantly affected. Increased glutathione peroxidase (GPx) activity seemed to compensate for a decrease in GPx1 protein due to enhanced degradation via the proteasome. Mass spectrometry analysis identified Lys-114 as a possible carbonylation target which provides a vestibule for the substrate H2O2 and thus enhances the enzymatic reaction.InnovationOxidative protein carbonylation has so far been associated with functional inactivation of modified target proteins mainly contributing to aging and age-related diseases. Here, we demonstrate that mild oxidative stress and subsequent carbonylation seem to activate protective cellular redox signaling pathways whereas severe oxidative stress overwhelms the cellular antioxidant defense leading to cell damage.ConclusionsThis study may contribute to a better understanding of redox homeostasis and its role in the development of diabetes and related vascular complications.

Are the impacts of carbon nanotubes enhanced in Mytilus galloprovincialis submitted to air exposure?

“…On the other hand, when mussels were contaminated the decrease of LPO levels under tidal regime may indicate that the limited presence of MWCNTs, only during high tide periods, caused a less stressful condition or the combination of air exposure and MWCNT contamination induced higher oxidative stress compared to organisms submersed the entire experiment in the presence of these which was surpassed by the activation of NPs antioxidant enzymes that eliminated ROS and prevented the occurrence of LPO. (Sultan et al, 2018). In fact, ROS may promote the oxidation of proteins, a process known as protein carbonylation (PC) which constitutes the most common type of PTM triggered by oxidative stress (Cattaruzza and Hecker, 2008;Suzuki et al, 2010 In general, the present results showed no alteration on PC levels in ).…”

Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications

“…The hindering mechanisms act through the poly-ADP-ribose polymerase (PARP) pathway, which alters GAPDH through polymers of ADP-ribose. Hyperglycemia provokes overproduction of ROS [ 99 ] and DNA single-strand cracks [ 100 ], both of which can stimulate PARP [ 101 ], thereby resulting in an alteration of GAPDH and a decrease of its activity [ 102 ] ( Figure 2 ).…”

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

“…In the mitochondrial matrix, superoxide dismutase (SOD) 2 reduces O 2 − into H 2 O 2 , a less toxic ROS [83]. Then, glutathione peroxidase (GPX) catalyzes the reduction of H 2 O 2 into H 2 O through the oxidation of reduced glutathione (GSH) into its oxidized form (GSSG) [84,85]. Catalase in the mitochondrial matrix can also convert H 2 O 2 into water and molecular oxygen [86,87].…”