Catalase and Superoxide Dismutase Conjugated with Platelet-Endothelial Cell Adhesion Molecule Antibody Distinctly Alleviate Abnormal Endothelial Permeability Caused by Exogenous Reactive Oxygen Species and Vascular Endothelial Growth Factor

Abstract

Reactive oxygen species (ROS) superoxide anion (O 2 . ) and hydrogen peroxide (H 2 O 2 ) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/ SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H 2 O 2 -induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H 2 O 2 in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O 2 . in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of specific ROS in vascular pathology and may be translated into remedies for these ROS-induced abnormalities.

Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway

“…As the important products of oxidative stress, ROS generation during cerebral ischemic injury was suggested to cause severe brain damage (Olmez and Ozyurt 2012). Previous studies have shown that incubation of endothelial cells with ROS promotes cellular contraction and increases the permeability of endothelial monolayers, finally causing endothelial cell death and further deterioration of BBB (Han et al 2011;Pun et al 2009). In this study, ROS levels were measured using flow cytometry analysis.…”

The effects of iron deficiency on the level of oxidative stress and antioxidant defenses in suckling piglets

“…The other haematological indices and iron concentration in blood plasma were also significantly lower in the experimental group compared to control. Oxidative stress has been defined as a disturbance of equilibrium between the production of reactive oxygen species and the antioxidant defence system (P i et al 2010) including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) (Han et al 2011). Increased lipid peroxidation has been associated with iron deficiency in rats and human patients (Kumerova et al 1998), but the topic remains controversial (Acharya et al 1991).…”

Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

“…Pretpostavljeni genoprotektivni mehanizam Sal B u pretretmanu naše studije mogao bi da bude povećanje intracelularnog antioksidativnog enzimskog kapaciteta (38). Upotreba kineske žalfije (Salvia miltiorrhiza), koja kao jedan od sastojaka ima Sal B, može da poveća aktivnost katalaze i glutation peroksidaze (39), dva enzima koja su odgovorna za konverziju vodonik-peroksida do vode i kiseonika (40).…”