Catalase overexpression impairs TNF‐α induced NF‐κB activation and sensitizes MCF‐7 cells against TNF‐α

Abstract

The pleiotropic cytokine tumor necrosis factor alpha (TNF-alpha) can induce apoptosis but also supports cell survival pathways. Among the possible anti-apoptotic mechanisms of TNF-alpha is the activation of the transcription factor NF-kappaB. Since reactive oxygen species (ROS) are assumed to contribute to TNF-alpha mediated cytotoxicity but can also facilitate NF-kappaB activation this study investigates the relationship between TNF-alpha treatment, NF-kappaB activation and the expression of the anti-oxidative enzyme catalase. TNF-alpha treatment caused downregulation of catalase expression in MCF-7, Caco-2 and Hct-116 cancer cell lines. Overexpression of catalase in MCF-7 cells, resulting in lower intracellular ROS levels upon challenge with H(2)O(2), caused a transient nuclear p65 translocation upon TNF-alpha treatment as compared to the sustained NF-kappaB activation in wild type cells. This was due to a lack of sufficient H(2)O(2) to co-stimulate NF-kappaB activation as demonstrated by the observation that addition of exogenous H(2)O(2) led to a second increase of NF-kappaB activity. The rapid decline of nuclear translocation of NF-kappaB in the catalase overexpressing cells resulted in a slower increase of NF-kappaB mediated reporter gene expression. These results indicate that TNF-alpha mediated downregulation of catalase expression and accordingly sufficient H(2)O(2) is required for appropriate function of the NF-kappaB dependent survival pathway.

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

“…This finding is consistent with a previous report, in which it was demonstrated that catalase levels declined significantly in vascular smooth muscle cells chronically exposed to lead (Ni et al, 2004). Catalase expression can be downregulated by lipopolysaccharide (Clerch et al, 1996), ionizing radiation (Ushakova et al, 1999;Nenoi et al, 2001), and tumor necrosis factor-alpha (Clerch and Massaro, 1992;Chovolou et al, 2003;Lupertz et al, 2008), which stimulated cell death or oxidative stress in the cells. Therefore, in this study, the downregulation of catalase was related to Pb-induced cell death in endothelial cells.…”

Intestinal Epithelial Cell Proteome from Wild-Type and TNFΔARE/WT Mice: Effect of Iron on the Development of Chronic Ileitis

“…51 Interestingly, an overexpression of catalase in MCF-7 (human breast adenocarcinoma cell line) cells resulted in improved elimination of intracellular ROS, decreased H 2 O 2 -mediated cytotoxicity, increased cell viability and impaired TNF-R induced NF-κB activation. 52 Consistent with these experimental findings, the up-regulation of catalase under dietary low-iron seems to have protective functions in primary IEC. In contrast to the ARE-comparison, the loss of catalase protein expression in the iron-adequate fed TNF ∆ARE group may cause increased H 2 O 2 accumulation.…”

Increased expression of TLR-2, COX-2, and SOD-2 genes in the peripheral blood leukocytes of opisthorchiasis patients induced by Opisthorchis viverrini antigen

“…Our result showed that SOD-2 was positively correlated with oxidantgenerating genes, suggesting its expression is the first line to catalyze ROS generation (Feng et al 1995). On the other hand, CAT expression was suppressed in both groups but more significantly lowered in the infected group, suggesting an increased oxidative stress by a decrease in anti-oxidant of CAT during the inflammatory response due to the detoxification function of hydrogen peroxide (H 2 O 2 ) (Lupertz et al 2008;Canonico et al 1977). An adaptive imbalance of antioxidant enzymes to genotoxic stress can be the procarcinogenic effect which has been proposed by Hofseth et al (2003).…”