The effects of methyl mercury binding to microtubules

Vogel, D.; Margolis, Robert L.; Mottet, N. Karle

doi:10.1016/0041-008x(85)90392-8

Cited by 121 publications

(47 citation statements)

References 28 publications

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“…This has been regarded as the cause of the increased frequency of polyploidy and aneuploidy in Allium and Drosophila (Ramel & Magnusson 1969, 1979, Fiskesjo 1988. Moreover, in vitro polymerization and depolymerization of microtubules is affected by MeHg (Vogel et al 1985). This could explain some of the multiple effects of MeHg on the cell cycle, including a lengthened G1 and decreased transition probability after short term exposure of cycling cells, and a G2 accumulation after a longer term exposure (Vogel et al 1986).…”

Section: Discussionmentioning

confidence: 97%

Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon

Amorim

Mergler

Bahia

et al. 2000

An. Acad. Bras. Ciênc.

105

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The mercury rejected in the water system, from mining operations and lixiviation of soils after deforestation, is considered to be the main contributors to the contamination of the ecosystem in the Amazon Basin. The objectives of the present study were to examine cytogenetic functions in peripheral lymphocytes within a population living on the banks of the Tapajós River with respect to methylmercury (MeHg) contamination, using hair mercury as a biological indicator of exposure. Our investigation shows a clear relation between methylmercury contamination and cytogenetic damage in lymphocytes at levels well below 50 micrograms/gram, the level at which initial clinical signs and symptoms of mercury poisoning occur. The first apparent biological effect with increasing MeHg hair level was the impairment of lymphocyte proliferation measured as mitotic index (MI). The relation between mercury concentration in hair and MI suggests that this parameter, an indicator of changes in lymphocytes and their ability to respond to culture conditions, may be an early marker of cytotoxicity and genotoxicity in humans and should be taken into account in the preliminary evaluation of the risks to populations exposed in vivo. This is the first report showing clear cytotoxic effects of long-term exposure to MeHg. Although the results strongly suggest that, under the conditions examined here, MeHg is both a spindle poison and a clastogen, the biological significance of these observations are as yet unknown. A long-term follow-up of these subjects should be undertaken.

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Section: Discussionmentioning

confidence: 97%

Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon

Amorim

Mergler

Bahia

et al. 2000

An. Acad. Bras. Ciênc.

105

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“…The arresting of the G2/Mphase because of microtubules being disrupted may be an important factor in MeHg leading to apoptosis . MeHg has long been known to be a potent inhibitor of microtubule polymerization, and this effect is presumably caused by the S-mercuration of the microtubules by MeHg (Abe et al, 1975;Sager et al, 1983;Vogel et al, 1985Vogel et al, , 1989. Vogel et al (1989) found that there is a class of binding sites that have high affinities for MeHg on tubulin and that MeHg binds to tubulin stoichiometrically within microtubules.…”

Section: The Disruption Of Microtubules 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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“…To date, MeHg has been shown to possess high affinity for tubulin sulfhydryl groups (Vogel et al, 1985), to depolymerize cerebral microtubules in vitro (Abe et al, 1975) and to directly inhibit in vitro microtubule assembly (Sager et al, 1983). Moreover, MeHg has been reported to promote microtubule disruption in several cell models, including human fibroblasts (Sager et al, 1983), mouse splenic lymphocytes (Roy et al, 1991), neuroblastoma (Prasad et al, 1979), glioma cells (Prasad et al, 1979;Miura et al, 1984) and embryonal carcinoma cells Wasteneys et al, 1988;Graff et al, 1993).…”

mentioning

confidence: 98%

Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury

et al. 2000

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Cerebellar granule cells (CGCs) are a sensitive target for methylmercury (MeHg) neurotoxicity. In vitro exposure of primary cultures of rat CGCs to MeHg resulted in a time- and concentration-dependent cell death. Within 1 hr exposure, MeHg at 5-10 microM caused impairment of mitochondrial activity, de-energization of mitochondria and plasma membrane lysis, resulting in necrotic cell death. Lower MeHg concentrations (0.5-1 microM) did not compromise cell viability, mitochondrial membrane potential and function at early time points. Later, however, the cells progressively underwent apoptosis and 100% cell death was reached by 18 hr treatment. Neuronal network fragmentation and microtubule depolymerization were detected as early as within 1.5 hr of MeHg (1 microM) exposure, long before the occurrence of nuclear condensation (6-9 hr). Neurite damage worsened with longer exposure time and proceeded to the complete dissolution of microtubules and neuronal processes (18 hr). Microtubule stabilization by taxol did not prevent MeHg-induced delayed apoptosis. Similarly ineffective were the caspase inhibitors z-VAD-fluoromethylketone and z-DEVD-chloromethylketone, the L-type calcium channel inhibitor nifedipine, the calcium chelator EGTA and BAPTA, and the NMDA receptor antagonist MK-801. On the other hand, insulin-like growth factor-I partially rescued CGCs from MeHg-triggered apoptosis. Altogether these results provide evidence that the intensity of MeHg insult is decisive in the time of onset and the mode of neuronal death that follows, i.e., necrosis vs. apoptosis, and suggest that cytoskeletal breakdown and deprivation of neurotrophic support play a role in MeHg delayed toxicity.

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The effects of methyl mercury binding to microtubules

Cited by 121 publications

References 28 publications

Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon

Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon

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

Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury

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