Induced resistance in cells exposed to repeated low doses of HO involves enhanced activity of antioxidant enzymes

Abstract

We have derived cells from the Chinese hamster V79 cell line by conditioning them with repeated low doses of hydrogen peroxide (H(2)O(2)). This mimics the physiological condition where cells are repeatedly exposed to low levels of oxidants. In an attempt to characterize such cells, we have exposed both conditioned cells (V79(C)) and the parental V79 cells (V79(P)) to different types of cytotoxic agents and compared their sensitivity to cell killing. The V79(C) cells were found to be stably resistant to killing by agents that produced toxicity through oxidative stress, e.g. H(2)O(2) and cisplatin. It was also found that the lipid peroxidation produced by these agents were considerably lower in the V79(C) cells. Thus, the difference in sensitivity could be due to lesser extent of damage to these cells. V79(C) cells had greater antioxidant defense through higher GSH content and greater activity of enzymes such as Cu-Zn superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which provided protection from damage. Enzyme activities were also assayed at different times after treatment with various cytotoxic agents; there was a relatively large increase in SOD activity which perhaps plays a key role in determining the resistance of the V79(C) cells to killing.

Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function

“…Previous studies have shown that oxidative stress can induce ceramide generation from sphingomyelin via nSMase activation and lead to accumulation of cholesterol esters which consequently results in cell death (Goldkorn et al 1998;Cutler et al 2002). In contrast, GSH, which is increased in oxidative stress-resistant cells (Bose Girigoswami et al 2005), has been shown to block nSMase activation (Rutkute et al 2007). Cutler et al (2004) showed that sphingomyelin levels decrease in aging mice in an ADvulnerable area, the middle frontal gyrus, but not in the relatively spared cerebellum, and observed a correlation between these changes with enhanced oxidative stress shown by the increased levels of lipid peroxidation products.…”

Hydrogen peroxide enhances phagocytosis ofPseudomonas aeruginosain hyperoxia

“…Although H 2 O 2 has been shown to alter actin interactions via oxidation of the thiol groups (Crowell et al, 1995), studies in this report indicate that moderate concentrations of H 2 O 2 can reduce actin carbonylation in hyperoxic macrophages ( Figure 5). Even though H 2 O 2 can cause oxidative damage, low doses of H 2 O 2 have been shown to be involved in enhanced activities of antioxidant enzymes (Bose Girigoswami et al, 2005). We have previously demonstrated that antioxidants, including superoxide dismutase, can rescue hyperoxia-suppressed macrophage functions (Morrow et al, 2007).…”

Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes

“…This method, called conditioning, has shown to often lead to an increased tolerance or total resistance of those cell populations against the toxin (Ramakrishnan et al, 2010). These resistant cell lines can then be further examined to find the protection-conferring genes (Alborzinia et al, 2011;Bose Girigoswami et al, 2005).…”

“…It has been proposed that H 2 O 2 resistant cell lines can be used to unravel novel H 2 O 2 protection-conferring genes (or more correctly, the proteins they code for), and that such novel genes can contribute to the development of novel neuroprotective drugs. To date, a number of studies have reported the generation of H 2 O 2 resistant cells (Andley and Spector, 2005;Bose Girigoswami et al, 2005;Spector et al, 2000;Spitz and Sullivan, 2010). One of them, a murine hippocampal HT22 cell line, was generated by Schaferet al (Schafer et al, 2004) and showed a cross-resistance to glutamate, while the simultaneously created glutamate resistant cell line showed a similar resistance against H 2 O 2 .…”

“…Chronic treatment of mammalian cells with H 2 O 2 has shown that cells are able to adapt to oxidative stress. The most common resistance mechanisms are based on an increase in glutathione GSH content or activity of antioxidative enzymes such as superoxide dismutase (SOD), catalase or glutathione peroxidase (GPX) (Bose Girigoswami et al, 2005;Cantoni et al, 1993;Spitz et al, 1992;Spitz et al, 1988b).…”