Redox regulation of manganese superoxide dismutase

Abstract

The importance of reactive oxygen species (ROS) or changes in cellular redox state in signal transduction and gene regulation is becoming increasingly evident. In this study, we tested the hypothesis that ROS are directly involved in the induction of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD) and mediate the induction of MnSOD by tumor necrosis factor-alpha (TNF-alpha). Pretreatment of human pulmonary adenocarcinoma cells H441 with the antioxidants N-acetyl-L-cysteine (NAC) and nordihydroguaiaretic acid (NDGA) blocked MnSOD induction by TNF-alpha, implicating ROS as a signaling agent in this pathway. Treatment of H441 cells with the exogenous oxidants hydrogen peroxide (H2O2) and diamide increased MnSOD mRNA, supporting the hypothesis that ROS directly affect expression of MnSOD. The temporal pattern of MnSOD induction differed for TNF-alpha and H2O2, suggesting distinct signaling pathways. DNA binding of two redox-sensitive transcription factors, NF-kappa B and activator protein (AP)-1, was evaluated. TNF-alpha increased nuclear factor (NF)-kappa B-DNA binding, an effect blocked by pretreatment with NAC. H2O2 did not alter NF-kappa B-DNA binding. There was no evidence of AP-1 binding in cells treated with either TNF-alpha or H2O2. We conclude that ROS directly alter MnSOD expression and are involved in the induction of MnSOD by TNF-alpha.

Redox Regulation of cAMP-responsive Element-binding Protein and Induction of Manganous Superoxide Dismutase in Nerve Growth Factor-dependent Cell Survival

“…the relative role of this factor in the induction of Mn-SOD by NGF with respect to other potential candidates such as nuclear factor B. However, even though the mechanisms involved are unclear, the evidence of Mn-SOD induction through a ROS-dependent cascade is biologically sound and in line with other findings that oxidants are inducers of antioxidant enzymes in both prokaryotic (52) and eukaryotic cells (53).…”

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

“…The expression of proinflammatory cytokines is tightly controlled by the transcription factor, NF-B (35), and NF-B is notably known to be activated by ROS (42,43). Carboxyalkylpyrroles, the end products of lipid peroxidation, activate NF-B via TLR2 stimulation and subsequent MyD88 recruitment (48).…”

“…NF-B is responsible for the expression of several cytokines under inflammation in the CNS, and ROS are known to regulate the activity of NF-B (42,43). Treatment of microglia with ROS or ROS-generating reagents increased the mRNA expression of TNF␣, IL-1␤, and SOD2 (data not shown).…”

Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

“…The augmentation in apoptotic cells may be due to an increased sensitivity of the opening of the mitochondria transition pore, which is a key event in the intrinsic pathway of apoptosis activated by oxidative stress (48). The up-regulation of Mn-SOD in the epidermis from the elderly is most likely triggered by increased ROS (49,50) derived from a combination of intrinsic changes related to longevity as well as environmental factors, primarily exposure to UV irradiation (photoaging) (Fig. 8).…”