Augmentation of antioxidant enzymes in vascular endothelium |
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| Affiliation: | 1. Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland;2. Department of Pharmacological Screening, Chair of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland;3. Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland;1. Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA;2. Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA;1. Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan;2. Pharmaceutical Education Support Center, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women''s University, 9-11-68 Koshien, Nishinomiya, Hyogo 663-8179, Japan;3. Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan;4. Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan;1. Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China;2. College of Life Sciences and Bioengineering, Beijing University of Technology, Beijing, China;1. Department of Psychological Sciences, School of Medicine and Health Sciences, University of Chieti, Chieti, Italy;2. CeSI-Met, University of Chieti, Chieti, Italy;3. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;4. University of Chinese Academy of Sciences, Shijingshan District, Beijing 100049, China |
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| Abstract: | The endothelium is a key site of injury from reactive oxygen species that can potentially be protected by the antioxidant enzymes superoxide dismutase and catalase. Large proteins, such as superoxide dismutase and catalase, do not readily penetrate cell membranes, which limits their efficacy in protecting cells from cellular reactions involving both intracellularly and extracellularly generated reactive oxygen species. Two methods are described that promote enzyme delivery to cultured endothelial cells and confer increased resistance to oxidative stress. The first method is to entrap the antioxidant enzymes within liposomes, which then become incorporated by endothelial cells and can increase enzyme specific activities by as much as 44-fold within 2 h. The second method involves covalent conjugation of polyethylene glycol (PEG) to superoxide dismutase and catalase, a technique that increases circulatory half-life and reduces protein immunogenicity. Conjugation of PEG to superoxide dismutase and catalase increased cellular-specific activities of these enzymes in cultured endothelial cells (but at a slower rate than for liposome entrapped enzymes) and rendered these cells more resistant to oxidative stress. Both liposome-mediated delivery and PEG conjugation offer an additional benefit over native superoxide dismutase and catalase because they can increase cellular antioxidant activities in a manner that can provide protection from both intracellular and extracellular superoxide and hydrogen peroxide. |
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