Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular antioxidant enzymes protect against damage caused by exposure to endogenous or exogenous prooxidants. Singlet oxygen ((1)O(2)) is a reactive form of oxygen that can be produced in vivo either in normal and pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. We hypothesized that photodynamically generated (1)O(2) would decrease the enzymatic activities of cellular antioxidants. To test this hypothesis, we treated cultured mouse epidermal keratinocytes with the photosensitizer Photofrin plus visible light to produce (1)O(2), and then measured CuZnSOD, MnSOD, and catalase activities with both ingel and spectrophotometric enzyme activity assays. Our results demonstrated that the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were significantly decreased after keratinocytes were treated with Photofrin plus visible light. By contrast, the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were unaffected in control cells treated with Photofrin only or visible light only. Despite the decreased levels of enzymatic activities, the protein levels of all three primary antioxidant enzymes remained constant after photodynamic treatment, as determined by Western blotting. L-Histidine, a (1)O(2) quencher, protected against the inactivation of cellular CuZnSOD, MnSOD, and catalase enzymes induced by photodynamically generated (1)O(2). The conclusion from these experiments is that the primary cellular antioxidant enzymes CuZnSOD, MnSOD, and catalase can be inactivated by photodynamically generated (1)O(2) in nucleated mammalian cells. These findings may be useful in the future development of antineoplastic adjuvant therapies that use photodynamic generation of (1)O(2) to inactivate antioxidant defenses with a goal of sensitizing tumor cells to prooxidant-generating drugs.
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PMID:Inactivation of primary antioxidant enzymes in mouse keratinocytes by photodynamically generated singlet oxygen. 1691 Jul 78

Superoxide, a reactive form of oxygen, can be produced in vivo either in normal and under pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. Photodynamic therapies (PDT), widely adopted in Dermatology and Oncology, are known to generate reactive oxygen species (ROS) and may contribute to structural alterations and oxidatively generated modifications of cellular antioxidants. We hypothesized that over-production of free radicals would decrease the enzymatic activities of endogenous cellular antioxidants. To test this hypothesis, keratinocytes were treated with the photosensitizer Photofrin plus visible light to produce free radicals and CuZnSOD and MnSOD activities were measured. Photodynamic treatment of keratinocytes increases malonylaldehyde production, nitrotyrosine staining and superoxide production. The enzymatic activities of CuZnSOD and MnSOD were significantly decreased after Photofrin plus visible light treatment. Our results suggest that the main cellular antioxidant system can be inactivated by photodynamically generated ROS. Pretreatment of keratinocytes with free radicals scavenger such as Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) was able to restore the endogenous antioxidant system activities, inhibiting the MDA formation, nitrotyrosine staining and superoxide formation. Antioxidant therapy could therefore be a useful tool in protecting healthy epidermal cells against common side effects induced by antitumor targeted therapies.
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PMID:Effect of MN (III) tetrakis (4-benzoic acid) porphyrin by photodynamically generated free radicals on SODs keratinocytes. 2415 29