Alterations in Superoxide Dismutase Isozymes by Methylmercury

Kumagai, Yoshio; Homma-Takeda, Shino; Shinyashiki, Masaru; Shimojo, N.

doi:10.1002/(sici)1099-0739(199708)11:8<635::aid-aoc625>3.3.co;2-c

Cited by 4 publications

(5 citation statements)

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“…It is recognized that unlike methylmercury ions, mercury ions are bifunctional and bind not only to sulfhydryl groups but also to amino groups (Webb 1966). Thus, a change in native form of Mn-SOD involving decreased enzyme activity could be initiated after covalent attachment of mercury ions to the protein through reactive amino acid residues including Cys196 (Kumagai et al 1997). In our preliminary study, it was found that mercury ions were covalently bound to the Mn-SOD precipitated during reaction with an excess amount of HgCl 2 and the ratio of moles of mercury bound to moles of Mn-SOD was more than 10 (Y. Noto et al, unpublished observation).…”

Section: Resultssupporting

confidence: 79%

“…In our preliminary study, it was found that mercury ions were covalently bound to the Mn-SOD precipitated during reaction with an excess amount of HgCl 2 and the ratio of moles of mercury bound to moles of Mn-SOD was more than 10 (Y. Noto et al, unpublished observation). We have previously reported that loss of activity of murine Mn-SOD caused by methylmercuric chloride is due to conformational change through covalent attachment to methylmercury ions without sedimentation (Shinyashiki et al 1996;Kumagai et al 1997). Therefore, the present study indicates that mercury ions and methylmercury ions inhibit murine Mn-SOD activity via different mechanisms.…”

Section: Resultsmentioning

confidence: 95%

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Difference between kidney and liver in decreased manganese superoxide dismutase activity caused by exposure of mice to mercuric chloride

Shimojo

Kumagai

Nagafune

2002

Archives of Toxicology

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Dysfunction of antioxidant enzymes caused by mercuric compounds is partially associated with substantial induction of oxidative stress. In the present study, changes in renal and hepatic enzyme activity of an antioxidant protein manganese superoxide dismutase (Mn-SOD) after exposure to mercuric chloride (HgCl(2)) were examined in ICR mice. Subcutaneous administration of HgCl(2) (0.25-3 mg/kg) resulted in a decrease in renal Mn-SOD activity in a dose-dependent manner, whereas the hepatic enzyme activity was unaffected following injection of HgCl(2). Mercury accumulation in the kidney was drastically higher (34-75 times) than that in the liver after HgCl(2) administration. Examining interactions of purified Mn-SOD with HgCl(2) indicated that mercury ions suppressed Mn-SOD activity by reduction of the native form. These results suggest that inorganic mercury can directly interact with murine Mn-SOD, resulting in decrease of the enzyme activity and that the HgCl(2)-mediated significant reduction of renal, but not hepatic, Mn-SOD activity in vivo appears to be associated with the tissue specificity for mercury accumulation.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 95%

Difference between kidney and liver in decreased manganese superoxide dismutase activity caused by exposure of mice to mercuric chloride

Shimojo

Kumagai

Nagafune

2002

Archives of Toxicology

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“…They found that the sensitivity of HeLa cells to MeHg was decreased by the overexpression of Mn-SOD, suggesting that the formation of superoxide anions in the mitochondria might be involved in the mechanism(s) involved in the cytotoxicity of MeHg. We have attempted to examine the mechanism involved in the relationship between Mn-SOD and MeHg (Kumagai et al, 1997;Shinyashiki et al, 1996). Levels of mRNA and protein synthesis for Mn-SOD were unaffected by MeHg administration.…”

Section: Oxidative Stress and S-mercurationmentioning

confidence: 99%

<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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“…Although levels of mRNA and protein synthesis of Mn-SOD were unaffected by MeHg administration, MeHg caused a facile reduction in the activity, and a drastic decrease in the native form, of Mn-SOD (but not of Cu,Zn-SOD) with purified enzyme preparations. It was subsequently shown that the S -mercuration of Mn-SOD, through Cys196, by MeHg results in a decrease in the enzyme activity in vivo [14]. Therefore, the selective inhibition of Mn-SOD activity caused by S -mercuration could play a critical role in MeHg-induced neurotoxicity because SOD protects the cell against oxidative stress by scavenging superoxide.…”

Section: S-mercuration Of Proteins By Mehgmentioning

confidence: 99%

The Role of the Keap1/Nrf2 Pathway in the Cellular Response to Methylmercury

Kumagai

Kanda

Shinkai

et al. 2013

Oxidative Medicine and Cellular Longevity

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Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins with reactive thiols, resulting in the formation of protein adducts. While such protein modifications, referred to as S-mercuration, are thought to be associated with the enzyme dysfunction and cellular damage caused by MeHg exposure, the current consensus is that (1) there is a cellular response to MeHg through the activation of NF-E2-related factor 2 (Nrf2) coupled to S-mercuration of its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), and (2) the Keap1/Nrf2 pathway protects against MeHg toxicity. In this review, we introduce our findings and discuss the observations of other workers concerning the S-mercuration of cellular proteins by MeHg and the importance of the Keap1/Nrf2 pathway in protection against MeHg toxicity in cultured cells and mice.

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Alterations in Superoxide Dismutase Isozymes by Methylmercury

Cited by 4 publications

References 0 publications

Difference between kidney and liver in decreased manganese superoxide dismutase activity caused by exposure of mice to mercuric chloride

Difference between kidney and liver in decreased manganese superoxide dismutase activity caused by exposure of mice to mercuric chloride

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

The Role of the Keap1/Nrf2 Pathway in the Cellular Response to Methylmercury

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