We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelia...

Radiation therapy of tumors of the head and neck region is compromised by dose limiting toxicity of normal tissues including the oral cavity and oropharyngeal mucosa. MnSOD-Plasmid Liposome (MnSOD-PL) intraoral gene therapy has been demonstrated to decrease normal tissue toxicity and also improve survival in mice with orthotopic SCC-VII squamous cell tumors on the floor of the mouth. Furthermor...

Endothelial progenitor cells (EPCs) play an essential role in angiogenesis but are functionally impaired in diabetes. We recently reported that decreased expression of manganese superoxide dismutase (MnSOD) critically contributes to diabetic EPC dysfunction. AMP-activated protein kinase (AMPK) activation has been shown to induce MnSOD and suppress hyperglycemia-induced mitochondrial ROS product...

Ding Y, Li Y, Zimmerman MC, Schultz HD. Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits. Am J Physiol Regul Integr Comp Physiol 298: R303–R311, 2010. First published November 18, 2009; doi:10.1152/ajpregu.00629.2009.—Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). Here we investigated th...

Proinflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha], and gamma-interferon [IFN-gamma]) initiate a variety of signal cascades in pancreatic beta-cells that affect the expression level of genes involved in both the destruction and the protection of the beta-cell. The generation of nitric oxide (NO) via the inducible NO synthase (iNOS) and oxygen free r...

Gene therapy on the basis of oncolytic adenovirus is a novel approach for human cancer therapeutics. We aim to investigate whether it will synergistically reinforce their antiovarian cancer activities when the combined use of ZD55-manganese superoxide dismutase (MnSOD) and cisplatin was performed. The experiments in vitro showed that ZD55-MnSOD enhances cisplatin-induced apoptosis and causes re...

Interleukin-1 (IL-1) and tumor necrosis factor (TNF) selectively induce mitochondrial manganese superoxide dismutase (MnSOD) production in various cell types. We have evaluated the capacity of tumor cells that overexpress MnSOD to recover from the cytostatic and cytotoxic effects of cytokines (IL-1 and TNF), chemotherapeutic agents, and ionizing irradiation. Clones of human melanoma cell line, ...

Mesalamine (5-ASA) is effective in the treatment of inflammatory bowel diseases. However, the mechanisms of action of 5-ASA remain unclear. IEC-6 and IRD-98, nontransformed rat small intestinal epithelial cell lines, were used to examine the effect of 5-ASA on the expression of manganese superoxide dismutase (MnSOD). Rats were given 5-ASA enemas to determine the effect on colonic MnSOD expressi...

The most important cellular protective mechanisms against oxidative stress are antioxidant enzymes. Their action is based on decomposal of reactive oxygen species (ROS) and their transformation to H2O2. Within the mitochondria manganese superoxide dismutase (MnSOD) affords the major defense against ROS. In this study we investigated tissue sections from 101 breast carcinomas for the immunohisto...

Manganous superoxide dismutase (MnSOD) scavenges potentially toxic superoxide radicals produced in the mitochondria. Tumor necrosis factor-alpha (TNF-alpha) was found to induce the messenger RNA for MnSOD, but not the mRNAs for other antioxidant or mitochondrial enzymes tested. The increase in MnSOD mRNA occurred rapidly and was blocked by actinomycin D, but not by cycloheximide. Induction of M...