Transgenic and mutant mice for oxygen free radical studies

Huang, Ting; Raineri, Ines; Eggerding, Faye A.; Epstein, Charles J.

doi:10.1016/s0076-6879(02)49335-4

Cited by 32 publications

(21 citation statements)

References 35 publications

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“…Aconitase activities were determined as described previously with minor modifications (Huang et al, 2002). Briefly, serial dilutions of each sample were separated on Cellogel s (300 mm thickness, Accurate Chemical & Scientific Corp., Westbury, NY, USA) at 130 V for 1 h in a potassium phosphate buffer (20 mM, pH 6.4) containing 3.7 mM citric acid.…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…Briefly, serial dilutions of each sample were separated on Cellogel s (300 mm thickness, Accurate Chemical & Scientific Corp., Westbury, NY, USA) at 130 V for 1 h in a potassium phosphate buffer (20 mM, pH 6.4) containing 3.7 mM citric acid. C-ACO and M-ACO were detected by activity staining of the gel (Huang et al, 2002). The enzyme activities were determined as a function of the band intensity and quantitated with image analysis software GelExpert (Nucleotech, San Mateo, CA, USA).…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…MnSOD activities were determined on a nondenaturing IEF gel (Ampholine PAGplate pH 3.5-9.5, Amersham Pharmacia Biotech Inc., Piscataway, NJ, USA) as described previously (Huang et al, 2002). Catalase and GPx activities were determined spectrophotometrically as described (Aebi, 1984;Flohe and Gunzler, 1984).…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…CuZnSOD (SOD1, Sod1) transgenic and mutant mice have been widely used to study the role of oxygen free radicals in different experimental systems (Huang et al, 2002;Kruidenier et al, 2003). Increased levels of CuZnSOD usually confer resistance to acute oxidative insults, whereas decreased expression renders mutant mice more sensitive to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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Mice deficient in CuZn superoxide dismutase (CuZn-SOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1À/À mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1À/À and age-matched þ / þ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1À/À mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.

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Section: Enzyme Assaysmentioning

confidence: 99%

Section: Enzyme Assaysmentioning

confidence: 99%

Section: Enzyme Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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“…Heterozygote transgenic mice carrying the human cytosolic SOD1 gene were bred with wildtype CD1 mice to produce pups that were both transgenic (Tg) and nontransgenic (WT) for hSOD1 (16,17). The heterozygotes expressed 3-fold higher SOD activity (18,19). Pups were identified at P6 by sampling tail blood using qualitative nondenaturing gel electrophoresis followed by nitroblue tetrazolium staining for the human SOD1 protein as previously described (17,19).…”

Section: Animalsmentioning

confidence: 99%

Manipulation of Antioxidant Pathways in Neonatal Murine Brain

et al. 2004

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To assess the role of brain antioxidant capacity in the pathogenesis of neonatal hypoxic-ischemic brain injury, we measured the activity of glutathione peroxidase (GPX) in both humansuperoxide dismutase-1 (hSOD1) and human-GPX1 overexpressing transgenic (Tg) mice after neonatal hypoxia-ischemia (HI). We have previously shown that mice that overexpress the hSOD1 gene are more injured than their wild-type (WT) littermates after HI, and that H 2 O 2 accumulates in HI hSOD1-Tg hippocampus. We hypothesized that lower GPX activity is responsible for the accumulation of H 2 O 2 . Therefore, increasing the activity of this enzyme through gene manipulation should be protective. We show that brains of hGPX1-Tg mice, in contrast to those of hSOD-Tg, have less injury after HI than WT littermates: hGPX1-Tg, median injury score ϭ 8 (range, 0 -24) versus WT, median injury score ϭ 17 (range, 2-24), p Ͻ 0.01. GPX activity in hSOD1-Tg mice, 2 h and 24 h after HI, showed a delayed and bilateral decline in the cortex 24 h after HI (36.0 Ϯ 1.2 U/mg in naive hSOD1-Tg versus 29.1 Ϯ 1.7 U/mg in HI cortex and 29.2 Ϯ 2.0 for hypoxic cortex, p Ͻ 0.006). On the other hand, GPX activity in hGPX1-Tg after HI showed a significant increase by 24 h in the cortex ipsilateral to the injury (48.5 Ϯ 5.2 U/mg, compared with 37.2 Ϯ 1.5 U/mg in naive hGPX1-Tg cortex, p Ͻ 0.008). These findings support the hypothesis that the immature brain has limited GPX activity and is more susceptible to oxidative damage and may explain the paradoxical effect seen in ischemic neonatal brain when SOD1 is overexpressed. (Pediatr Res 56: 656-662, 2004) Abbreviations CCA, common carotid artery GPX, glutathione peroxidase GSH, glutathione HI, hypoxia-ischemia P, postnatal day red-ox, oxidation-reduction reaction ROS, reactive oxygen species SOD1, copper-zinc superoxide dismutase Tg, transgenic WT, wild-typeThe developing brain faces unique challenges from oxidative stress, and has responses to injury and protective mechanisms that are different from the mature nervous system. The developmental profile of the activity of the endogenous antioxidant enzymes SOD1 and selenium-dependent GPX have been described for both rats (1-3) and mice (4). In the mouse brain, GPX activity is almost exclusively due to the classic, cellular glutathione peroxidase GPX1 (EC 1.11.1.9) (5). In the CD1 mouse, the outbred background strain used in this study, SOD1 activity decreases around the time of birth, and then remains unchanged to weaning. GPX activity, on the other hand, rises steeply around birth but declines sharply in the first few days of life and then remains low through weaning. Protein levels for both enzymes, however, show a steady increase during early development (4). We have shown that, in the CD1 mouse brain, adult levels of GPX activity are reached by weaning (6). Therefore, maturational differences may impact the response of the newborn brain to injury. It has been shown that the adult and juvenile brain attempts to compensate during oxidative stress in response to stroke (...

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Free Radicals in Biochemistry and Medicine

Halliwell

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Transgenic and mutant mice for oxygen free radical studies

Cited by 32 publications

References 35 publications

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

Manipulation of Antioxidant Pathways in Neonatal Murine Brain

Free Radicals in Biochemistry and Medicine

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