Antioxidant enzyme activities in normal and transformed mouse liver cells

Abstract

Copper- and zinc-containing superoxide dismutase (CuZnSOD), manganese-containing superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPX, both Se-dependent and Se-independent), and glutathione reductase (GR) were measured in normal, nitrosoguanidine-transformed and SV40-transformed mouse liver cells in culture, as well as in mouse liver homogenates. Enzyme activities were compared on the basis of 3 different endpoints: per mg protein, per mg DNA, and per 10(6) cells. Except for GR, activity of all the measured anti-oxidant enzymes was much higher in vivo than in vitro. All of the anti-oxidant enzyme activities were lower in general in the 2 transformed cell lines than in the in vitro normal cell line, except Cu-ZnSOD, which showed little change. However, MnSOD was the only enzyme which showed lowered activity in both transformed cell lines, no matter what endpoint was used. This finding is in agreement with previous work showing lowered MnSOD activity in tumor cells.

Potent Anti-tumor Effects of an Active Site Mutant of Human Manganese-Superoxide Dismutase

“…This assumption is further substantiated by the observation that Mn-SOD activity is generally low in cancer cells (20,21), suggesting that the oncogenic phenotype may be associated with or a consequence of lowered H 2 O 2 levels. To test the anti-proliferative effects of H30N overexpression in vivo, A549 cells were transduced with a bicistronic retroviral vector (pBMN-Mn-SOD-IRES-eGFP, Fig.…”

“…The product-inhibited state of Mn-SOD has been conserved from bacteria to man with the emergence of the inhibited form appearing 30-fold more rapidly for the human enzyme (11). In addition, in mammals, Mn-SOD has been postulated to function as a tumor suppressor gene (16 -19), with its expression and activity being significantly reduced in many cancers (20,21). Overexpression of Mn-SOD in several human cancer cell lines leads to reversion of the malignant phenotype with a decrease in cell proliferation (16 -19), which is thought to be mediated by H 2 O 2 , a potential signaling molecule (22)(23)(24) and primary product of Mn-SOD catalysis (2).…”

Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

“…release, which can be due to a negative (inhibitory or inactivating) influence of tumour cells. It is known that cancer cells may produce several factors that inactivate toxic mediators, including SOD (Sun et al, 1989). Transforming growth factor β (TGF-β), produced by tumour cells, may also be responsible for the inhibition of O 2 -.…”

Role of glycolysis inhibition and poly(ADP‐ribose) polymerase activation in necrotic‐like cell death caused by ascorbate/menadione‐induced oxidative stress in K562 human chronic myelogenous leukemic cells

“…3 In addition to this high energetic dependence, cancer cells generally exhibit a poor antioxidant status. [4][5][6] Therefore, we developed a novel strategy consisting of the generation of an oxidative stress by the use of a combination of sodium ascorbate (vitamin C) and menadione (vitamin K 3 ). 7 In this strategy, a redox cycle is initiated by electron transfer from ascorbate (AscH 2 ) to quinone (Q) as shown in the next equations:…”