Induction of synthesis of manganous superoxide dismutase in L‐M(pNtnF) cells carrying an inducible TNF gene

Abstract

Based on findings that the cytotoxic effects of tumor necrosis factor (TNF) are closely related to levels of intracellular oxygen radicals, and on the results of TNF gene transfection studies, the hypothesis was made that endogenous TNF (enTNF) acts as a protective factor against exogenous TNF by inducing inhibitors or scavengers of oxygen radicals. In order to test this hypothesis, we investigated the intracellular levels of manganous superoxide dismutase (MnSOD) and glutathione (GSH) in L-M(pNTnF) cells carrying a TNF gene induced by dexamethasone (DM). When L-M(pNTnF) cells were treated with DM they expressed enTNF, and acquired resistance to exogenous TNF. There was no change in the GSH concentration after enTNF induction, but a 1.9- to 3.9-fold increase in MnSOD levels was noted. Our findings suggest that enTNF exerts its protective function against the cytocidal effect of exogenous TNF by inducing MnSOD production.

Negative Regulation of JNK Signaling by the Tumor Suppressor CYLD

“…This result indicates that the loss of CYLD is sufficient for triggering a low level of constitutive cell signaling. However, because cell lines may secrete a low level of cytokines (51), it is also possible that the constitutive kinase activity in CYLD knockdown cells is caused by the stimulatory action of endogenous cytokines. Nevertheless, these findings suggest that CYLD is a critical signaling regulator that prevents aberrant activation of JNK and IKK.…”

Molecular mechanisms of tumor necrosis factor‐induced cytotoxicity

“…Indeed, some TNF-induced proteins have been identified which can partially inhibit TNF cytotoxicity when overexpressed in particular cell lines [32-351. The observation that at least two phenotypically different sublines can be derived from L929 cells, suggests the existence of different resistance mechanisms within one single cell line [36]. Interestingly, transfection of TNFsensitive L929 cells with the TNF gene under a constitutive promoter induces TNF resistance by downregulation of the receptors; how the latter effect is brought about, is still under investigation [19,37].…”

Resistance to Tumor Necrosis Factor-α (TNF-α)-induced Apoptosis in Rat Hepatoma Cells Expressing TNF-α Is Linked to Low Antioxidant Enzyme Expression

“…4) TNF-␣ supports (a) survival pathway(s), supposedly via the formation of antiapoptotic proteins. Development of resistance against TNF-␣-induced cytotoxicity has been demonstrated in a variety of experimental models, including the repeated administration of exogenous TNF-␣ to cultured cells (3) and animals (4,5) or the overexpression of endogenous TNF-␣ in cultured cells (6,7).…”