Modulation of antioxidant enzymes, reactive oxygen species, and glutathione levels in manganese superoxide dismutase-overexpressing NIH/3T3 fibroblasts during the cell cycle

Within many different cytotoxic activities of heavy metals in plant cells, one of the most important is connected with reactive oxygen species (ROS) generation. Mechanism of plant cell defense against reactive oxygen species and free radicals has a comprehensive character. The aim of presented paper is characterization of changes in mitochondrial manganese superoxide dismutase (MnSOD) gene transcript level that occurred in bread wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) seedlings during copper and manganese treatment. Our results show down-regulation of MnSOD expression in most cases after the oxidative burst evoked by copper excess. Manganese treatment, on the other hand, caused differential reaction of tested material indicating the substantial impact of cultivar genetic background in molecular response to the same stress-inducing conditions.

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Manganese Superoxide Dismutase Attenuates Cisplatin-Induced Renal Injury: Importance of Superoxide

Journal of the American Society of Nephrology ◽

10.1681/asn.v12122683 ◽

2001 ◽

Vol 12 (12) ◽

pp. 2683-2690 ◽

Cited By ~ 1

Author(s):

Christopher A. Davis ◽

Harry S. Nick ◽

Anupam Agarwal

Keyword(s):

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Renal Injury ◽

Manganese Superoxide Dismutase ◽

Cell Injury ◽

Reactive Oxygen ◽

Annexin V ◽

Oxygen Species ◽

Renal Epithelial Cell ◽

Manganese Superoxide

ABSTRACT. Cisplatin is a potent chemotherapeutic agent that is used to treat many human malignancies. Unfortunately, in addition to side effects such as ototoxicity, anaphylaxis, and bone marrow suppression, a significant percentage of patients receiving cisplatin develop severe nephrotoxicity. Mitochondrial dysfunction that is mediated via the generation of reactive oxygen species has been implicated in the pathogenesis of cisplatin-induced renal injury. To address the mechanism, it was hypothesized that overexpression of antioxidant enzymes, such as mitochondria-localized manganese superoxide dismutase (MnSOD) or mitochondria-targeted catalase (mito-Cat), would be cytoprotective in cisplatin-induced cell injury. To this end, human MnSOD or a mito-Cat vector were stably transfected into human embryonic kidney 293 cells. Cells that overexpressed MnSOD exhibited significantly less cell rounding and detachment compared with both mito-Cat and vector controls after exposure to 20 μM cisplatin. Cell injury as assessed by DNA fragmentation and annexin V binding assays was significantly decreased in the cells that overexpressed MnSOD compared with vector alone and mito-Cat. In addition, elevated levels of MnSOD were strongly associated with increased clonogenic potential after cisplatin challenge. Thus, overexpression of MnSOD, and not catalase, protects against cisplatin-induced renal epithelial cell injury. These results demonstrate the importance of reactive oxygen species in the mechanism that underlies cisplatin-induced renal injury and specifically implicate the superoxide radical, and not hydrogen peroxide, as the mediator.

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