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CORM‐3‐derived CO attenuates oxidative stress in vascular endothelial cells in SOD‐activity independent manner
Author(s) -
Mizuguchi Shinjiro,
Stephen Jancy,
Katada Kazuhiro,
Capretta Alfredo,
Potter Richard F,
Fraser Douglas F,
Cepinskas Gediminas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.235.8
Subject(s) - superoxide dismutase , oxidative stress , chemistry , reactive oxygen species , corm , endothelial stem cell , biochemistry , enzyme , in vitro , microbiology and biotechnology , biology , agronomy
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).