Methylmercury Poisoning Induces Oxidative Stress in the Mouse Brain

Yee, Simon; Choi, BongKyoo

doi:10.1006/exmp.1994.1017

Cited by 93 publications

(40 citation statements)

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“…MeHg exposure increases ROS generation in the nervous system, both in vivo (Ali et al, 1992;Yee and Choi, 1994) and in vitro (Bondy and McKee, 1990;Shanker and Aschner, 2003;Yee and Choi, 1996;Gassó et al, 2001;Limke and Atchison, 2002;Sarafian et al, 1994;Shnaker et al, 2005;Mundy and Freudenrich, 2000), suggesting the key role of oxidative stress in MeHg-neurotoxicity.…”

Section: Resultsmentioning

confidence: 99%

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

et al. 2011

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-The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.

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Section: Resultsmentioning

confidence: 99%

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

et al. 2011

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“…We summarize the effect MeHg has on these antioxidant enzymes below. Yee and Choi (1994) found a marked decrease in the total SOD activity in mouse brains when the mice had been treated with MeHg for a prolonged period (at 2.5 mg/kg/day for 7 days). The authors didn't determine which isozyme was involved in the enzyme loss, but eukaryotic cells contain two types of SODs, copper and zinc SOD (Cu,Zn-SOD) and manganese SOD (Mn-SOD).…”

Section: Oxidative Stress and S-mercurationmentioning

confidence: 95%

<i>S</i>-Mercuration of cellular proteins by methylmercury and its toxicological implications

2014

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-The accumulation of methylmercury (MeHg) through the daily consumption of large predatory fish poses potential health risks. MeHg has been found to cause Minamata disease, but the full nature of MeHg toxicity remains unclear. Because of its chemical properties, MeHg covalently binds to cellular proteins through their reactive thiols, referred to as S-mercuration, resulting in the formation of protein adducts. In this review, we summarize how the S-mercuration of cellular proteins could be involved in the major mechanisms that have been suggested to underlie MeHg toxicity. Additionally, we introduce our attempts to identify cases of S-mercuration for the research to reveal the true nature of MeHg toxicity.

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“…3 The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been clarified both in vitro (5-10) and in vivo (11)(12)(13). Failure to protect cells against the early oxidative stress triggers subsequent ER stress and apoptosis (9).…”

Section: Methylmercury (Mehg)mentioning

confidence: 99%

Post-transcriptional Defects of Antioxidant Selenoenzymes Cause Oxidative Stress under Methylmercury Exposure

Usuki¹,

Yamashita

Fujimura

2011

Journal of Biological Chemistry

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Methylmercury (MeHg) toxicity is a continuous environmental problem to human health. The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been clarified, but the molecular mechanisms underlying MeHg-mediated oxidative stress remain to be elucidated. Here we demonstrate a post-transcriptional effect of MeHg on antioxidant selenoenzymes by using a MeHg-susceptible cell line. MeHginduced selenium deficiency leads to failure of the recoding of a UGA codon for selenocysteine and results in degradation of the major antioxidant selenoenzyme glutathione peroxidase 1 (GPx1) mRNA by nonsense-mediated mRNA decay (NMD), a cellular mechanism that detects the premature termination codon (PTC) located 5-upstream of the last exon-exon junction and degrades PTC-containing mRNAs. In contrast, thioredoxin reductase 1 (TrxR1), another antioxidant selenoenzyme of the thioredoxin system, was likely skipped by NMD because of a UGA codon in the last exon. However, TrxR1 activity was decreased despite mRNA up-regulation, which was probably due to the synthesis of aberrant TrxR1 protein without selenocysteine. Changes in selenoenzyme GPx1 and TrxR1 mRNAs were observed earlier than was the incidence of oxidative stress and up-regulation of other antioxidant enzyme mRNAs. Results indicated that the MeHg-induced relative selenium-deficient condition affects the major antioxidant selenoenzymes GPx1 and TrxR1 through a post-transcriptional effect, resulting in the disturbance of cellular redox systems and the incidence of oxidative stress. Treatment with ebselen, a seleno-organic compound, effectively suppressed oxidative stress and protected cells against MeHg-induced relative selenium deficiency and cytotoxicity.

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Methylmercury Poisoning Induces Oxidative Stress in the Mouse Brain

Cited by 93 publications

References 0 publications

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

<i>S</i>-Mercuration of cellular proteins by methylmercury and its toxicological implications

Post-transcriptional Defects of Antioxidant Selenoenzymes Cause Oxidative Stress under Methylmercury Exposure

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