Resistance of SOD-Transgenic Mice to Oxidative Stress

Epstein, Charles J.; Chan, Pak H.; Cadet, Jean Lud; Carlson, Elaine J.; Chen, S.; Chu, Luke L. H.; Fahn, Stanley; Jackson‐Lewis, Vernice; Kinouchi, Hiroyuki; Kostić, Vladimir; Kujirai, Kayoko; Mizui, A.; Naini, A.; Przedborski, Serge; Yang, Guo‐Yuan

doi:10.1007/978-3-642-84842-1_9

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…It could be argued, nevertheless, as gluta- mate receptor blockers also attenuate METH-induced toxicity (Sonsalla et al, 1989) that release of excitatory amino acids must also play an important role in the manifestations of the deleterious effects of this drug. This argument does not detract from the present results but hints at the notion that free radical-induced changes may constitute a common pathway for the causation of damage in the CNS (see Epstein et al, 1992;Dawson et al, 1993). The recent report that stimulation of glutamate receptors generates the superoxide radical provides further support for this notion (Lafon-Cazal et al, 1993).…”

Section: Discussionsupporting

confidence: 63%

“…In summary, the present data and those of others support the notion that free radicals may play a role in the neurotoxicity of the amphetamines. The data accumulated with the SOD-Tg mice (Epstein et al, 1992;Przedborski et al, 19926;Cadet et al, 1993) appear to indicate that several pathological states that affect the CNS may be secondary to the deleterious effects of oxygen-based radicals (Cadet, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…Using mice similarly generated, it has recently been shown that the toxic effects of MPTP on the nigrostriatal DA pathway can be prevented (Przedborski et al, 19926). These SOD-Tg mice, which have very high levels of intracellular CuZnSOD (Przedborski et al, 1992a), are also protected against glutamate-and 0,-induced neurotoxicity (Epstein et al, 1992). In contrast, another line of Tg mice that overexpress the extracellular SOD show increased 0,based toxicity (Oury et al, 1992).…”

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confidence: 99%

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Rapid Communication: Attenuation of Methamphetamine‐Induced Neurotoxicity in Copper/Zinc Superoxide Dismutase Transgenic Mice

Cadet

Sheng

Ali

et al. 1994

Journal of Neurochemistry

247

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Administration of methamphetamine (METH) to rats and nonhuman primates causes loss of terminals in the nigrostriatal dopaminergic system. The mechanism by which METH causes its neurotoxicity is not known. To evaluate further the role of oxyradicals in METH‐induced neurotoxicity, we have tested its effects in CuZn superoxide dismutase (SOD) transgenic (Tg) mice, which express the human CuZnSOD gene. In non‐Tg mice, acute METH administration causes significant decreases in levels of dopamine (DA) and 3, 4‐dihydroxyphenylacetic acid (DOPAC) in the striata and cortices of non‐Tg mice. In contrast, there were no significant decreases in cortical or striatal DA in the SOD‐Tg mice. The effects of METH on DOPAC were also attenuated in both structures of these SOD‐Tg mice. Chronic METH administration caused decreases in levels of striatal DA and DOPAC in the non‐ Tg mice, whereas the SOD‐Tg mice were not affected. These results suggest that METH‐induced dopaminergic toxicity in mice may be secondary to increased production of reactive oxygen species such as the superoxide radical.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Rapid Communication: Attenuation of Methamphetamine‐Induced Neurotoxicity in Copper/Zinc Superoxide Dismutase Transgenic Mice

Cadet

Sheng

Ali

et al. 1994

Journal of Neurochemistry

247

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“…The existence of indigenous oxidative stress within the cell depends, among other factors, on the ratio between the rate of superoxide production and amount of Cu/Zn SOD present (40). Therefore, lesions caused by various exogenous insults could either be ameliorated or worsened, as was indeed the case in transfected-Cu/Zn SOD cells (13,19,20,41) and Tg-Cu/Zn SOD mice (42)(43)(44)(45)(46)(47)(48)(49) (38). This exchanger plays a significant role in extruding intraneuronal Ca2+; when this action is inhibited, glutamate neurotoxicity is potentiated.…”

Section: Methodsmentioning

confidence: 98%

Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons.

Bar-Peled

Korkotian

Segal

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

105

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(24).We previously investigated the possible involvement of Cu/Zn SOD overproduction in cell damage through the use of cellular and animal model systems. We found that stably transfected cells overexpressing Cu/Zn SOD exhibited substantially increased lipid peroxidation (13) and had a specific lesion that affects the chromaffin granule's proton pump, which plays an important role in the uptake of neurotransmitters into the vesicles (14). In the transgenic-Cu/Zn SOD (Tg-Cu/Zn SOD) mice, a similar defect was also identified in an analogous organelle, the platelet's dense granule, which is responsible for the uptake and storage of blood serotonin (17). It was also found that Tg-Cu/Zn SOD mice have certain thymus and bone marrow abnormalities that resemble the thymic defects in children with DS (18). These findings suggested that overexpression of Cu/Zn SOD in transgenic mice can indeed cause certain physiological abnormalities similar to those found in DS. These findings also indicated that defects caused by increased Cu/Zn SOD can have a highly specific subcellular target, and thus serve as a paradigm for how alterations in Cu/Zn SOD expression could cause oxidative stress mediated cell injury leading to neurodegenerative disease like ALS (for review, see ref. 25). In this context, it is important to note that the neuromuscular junctions of TgCu/Zn SOD mice display significant abnormalities and morphological changes including withdrawal and destruction of some terminal axons and development of multiple small terminals (15,16,26). Some of these subclinical changes are reminiscent of the pathology observed in transgenic mice with ALS-like disease, which was generated by overexpression of a mutated Cu/Zn SOD gene bearing familial ALS mutations (see ref. 25 and references therein).In the present study, we used cultured neurons from TgCu/Zn SOD mice to investigate the relation between increased expression of Cu/Zn SOD and kainic acid (KA)-induced exitotoxicity, with the aim of gaining insight into the role of altered Cu/Zn SOD expression and oxidative stress in neuronal death. MATERIALS AND METHODSTg-Cu/Zn SOD Mice and Primary Brain Cultures. Three independently produced strains of Tg-Cu/Zn SOD mice

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“…The EcoRI-BamHI DNA fragment contains the entire SOD-1 gene, including the promoter sequences required for expression in transfected cells. 10,11 In the heterozygous SOD-1 transgenic mice designated as TgHS/SF 218/3, a 3-fold increase in CuZn-SOD activity has been observed in all brain regions including the cerebral cortex, where CuZn-SOD levels were 7.9Ϯ0.5 and 22.7Ϯ1.41 units per milligram protein in nontransgenic and SODtransgenic mice, respectively. 12 Neurons, astroglia, and cerebral vessels were all stained immunocytochemically for a polyclonal antibody against SOD-1, suggesting that SOD-1 immunoreactivity is expressed in all brain cells in the transgenic mice.…”

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confidence: 99%

Amelioration of Vasospasm After Subarachnoid Hemorrhage in Transgenic Mice Overexpressing CuZn–Superoxide Dismutase

Kamii

Kato

Kinouchi

et al. 1999

Stroke

129

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Background and Purpose-To clarify the effect of superoxide dismutase (SOD) on vasospasm after subarachnoid hemorrhage (SAH), we investigated sequential changes in arterial diameter after SAH in transgenic mice overexpressing CuZn-SOD (SOD-1). Methods-SOD-transgenic mice and nontransgenic littermates (35 to 40 g) were subjected to SAH produced by endovascular perforation of left anterior cerebral artery. At 4 hours and 1, 3, 7, and 14 days after SAH, the mice were perfused with 10% formalin and consequently with a mixture of carbon black and 10% gelatin to cast all vessels. Vasospasm was evaluated by measuring the diameter of the left middle cerebral artery (MCA) with a microscope. Results-In nontransgenic mice, the diameter of the MCA on day 3 after SAH (110.5Ϯ20.5 m [meanϮSD]; nϭ16) was significantly reduced compared with that without SAH (138.5Ϯ14.5 m; nϭ12) (PϽ0.01). Moreover, on day 3 after SAH, the diameter of the MCA in SOD-transgenic mice (127.9Ϯ20.2 m; nϭ20) was significantly larger than that in nontransgenic mice (110.5Ϯ20.5 m; nϭ16) (PϽ0.05). Conclusions-These results suggest that SOD is effective on the amelioration of vasospasm after SAH and that oxygen free radicals, particularly superoxide, play an important role in the pathogenesis of vasospasm after SAH. (Stroke. 1999;30:867-872.)Key Words: free radicals Ⅲ mice, transgenic Ⅲ subarachnoid hemorrhage Ⅲ superoxide dismutase Ⅲ vasospasm E rythrocytes are essential for causing vasospasm, and oxyhemoglobin released from erythrocytes in the subarachnoid clot is believed to be a most potent trigger of vasospasm. 1,2 However, the pathophysiology of cerebral vasospasm after subarachnoid hemorrhage (SAH) still remains unclear. Recently, 2 major derangements in the cerebral artery have been indicated as a cause for cerebral vasospasm after SAH. One is augmentation of contraction, which is protein kinase C (PKC) dependent, and the other is suppression of dilation, which is mediated by endothelium-derived relaxing factor/nitric oxide (NO). 3 Oxygen free radicals are involved in both systems; active oxygens can activate the PKC system and lead to lipid peroxidation through activation of phospholipase A 2 , 4 and superoxide (O 2 Ϫ ) is known to inactivate NO, 5 resulting in the occurrence of vasospasm after SAH. Therefore, superoxide dismutase (SOD), an enzyme converting O 2 Ϫ to hydrogen peroxide (H 2 O 2 ), could prevent contraction of the cerebral artery after SAH. Experiments in vivo, however, have not always proven the efficacy of SOD in preventing vasospasm after SAH. Kamiyama et al 6 See Editorial Comment, page 872initially showed that SOD is effective against vasospasm induced by oxyhemoglobin in cats. In addition, intracisternal injection of SOD reduced endothelial injury and prevented the occurrence of vasospasm in a rabbit SAH model. 7 However, intrathecal administration of both SOD and catalase failed to protect against oxyhemoglobin-induced vasospasm in monkeys. 8 The discrepancy in the effect of SOD on vasospasm after SAH may result from difference...

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Resistance of SOD-Transgenic Mice to Oxidative Stress

Cited by 8 publications

References 30 publications

Rapid Communication: Attenuation of Methamphetamine‐Induced Neurotoxicity in Copper/Zinc Superoxide Dismutase Transgenic Mice

Rapid Communication: Attenuation of Methamphetamine‐Induced Neurotoxicity in Copper/Zinc Superoxide Dismutase Transgenic Mice

Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons.

Amelioration of Vasospasm After Subarachnoid Hemorrhage in Transgenic Mice Overexpressing CuZn–Superoxide Dismutase

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