Abstract
Our previous studies indicate that CO derived from CO‐releasing molecule, CORM‐3, while suppressing PMN transendothelial migration at the same time amplifies oxidative stress in PMN, whereas oxidative stress in vascular endothelial cells (HUVEC) is effectively suppressed by CORM‐3. However, the mechanisms of such opposing effects of CO with respect to ROS production are unknown.In this study we assessed the effects of CORM‐3‐derived CO on modulation of the antioxidant enzyme, superoxide dismutase (SOD), activity in an in vitro model of endotoxemia. To this end, HUVEC were stimulated with LPS (1μg/ml) for 1–4h in the presence or absence of CORM‐3 (100μM) and assessed for production of ROS, activation of NFκB and expression of adhesion molecule ICAM‐1. In parallel, SOD activity in cell lysates (cell‐associated SOD) and supernatants (soluble SOD) were also assessed.The obtained results indicate that LPS‐induced increase in ROS production, activation of NFκB and ICAM‐1 expression were effectively reduced by CORM‐3. Interestingly, CORM‐3‐dependent suppression of ROS production was not associated with increased SOD activity. On the contrary, CORM‐derived CO attenuated SOD activity in both, cell lysates and supernatants, and in an assay employing purified SOD1 enzyme, indicating that CORM‐3‐derived CO negatively regulates SOD activity in cultured vascular endothelial cells (HSFO‐NA6171; IRF‐025‐09).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.