Ubiquitin‐proteasome system is responsible for the protection of yeast and human cells against methylmercury

Hwang, Gi Wook; Furuchi, Takemitsu; Naganuma, Akira

doi:10.1096/fj.01-0899fje

Cited by 49 publications

(43 citation statements)

References 31 publications

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“…MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4)(5)(6)(7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9)(10)(11).…”

Section: T Oxic Organic Mercury Compounds Worry Many Communitiesmentioning

confidence: 99%

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

Korbas

Blechinger

Krone

et al. 2008

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

126

112

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Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos.methylmercury ͉ thimerosal ͉ x-ray fluorescence mapping ͉ eye lens T oxic organic mercury compounds worry many communities worldwide, yet the detailed mechanisms underlying their transport and toxicity remain uncertain (1). These neurotoxic compounds are particularly insidious due to the latency in onset of toxic symptoms and have caused several devastating masspoisonings of humans. Adults are affected, but exposure in utero has resulted in severe consequences such as microcephaly, cerebropalsy, seizures, and mental retardation. Methylmercury (MeHg) compounds are actively transported across cell membranes (2) although not, as originally thought, by molecular mimicry of methionine (3). Beyond this, however, our knowledge of the mechanisms underlying organic mercury (Hg) toxicity is fragmentary. MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4-7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9-11).Zebrafish (Danio rerio) are common model organisms for the study of embryonic development, and have found increasing use in vertebrate toxicology (12). While embryonic and larval zebrafish previously have been used to study the toxic effects of MeHg exposure at the whole body (13,14) and at the molecular level (15), there are no available data on MeHg uptake and accumulation with respect to different tissues and organs. Such information is critical to properly integrate information on tissue and cell specific impacts of Hg with uptake and accumulation of the metal at the whole animal level. We present herein a novel approach to the investigation of heavy-metal toxicity using synchrotron x-ray fluorescence imaging (16) to directly image metal localization within zebrafish larvae and to observe remarkable differential accumulation of organic Hg using this technique. Strikingly, we find that both methyl and ethyl Hg derivatives are concentrated to the greatest degree in lens epithelium with lower levels present in the brain, optic nerve, and other organs....

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Section: T Oxic Organic Mercury Compounds Worry Many Communitiesmentioning

confidence: 99%

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

Korbas

Blechinger

Krone

et al. 2008

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

126

112

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“…However, under in-vivo conditions toxic effects of MeHg may be counterbalanced by a proteasome-mediated protection. Hwang et al (2002) and Hwang (2011) demonstrated in yeast and human cell lines that enhanced resistance is mediated through enhanced expression of Cdc34 or Rad23 proteins which are important for ubiquitination, and accordingly, proteasomal degradation. Our study indicates that in crustaceans the exposure to inorganic mercury may suppress also in-vivo significantly the intracellular protein degradation.…”

Section: Discussionmentioning

confidence: 99%

The proteasomes of two marine decapod crustaceans, European lobster (Homarus gammarus) and Edible crab (Cancer pagurus), are differently impaired by heavy metals

Götze

Bose

Sokolova

et al. 2014

Comparative Biochemistry and Physiology Part C: Toxicology &

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The intracellular ubiquitin-proteasome system is a key regulator of cellular processes involved in the controlled degradation of short-living or malfunctioning proteins. Certain diseases and cellular dysfunctions are known to arise from the disruption of proteasome pathways. Trace metals are recognized stressors of the proteasome system in vertebrates and plants, but their effects on the proteasome of invertebrates are not well understood. Since marine invertebrates, and particularly benthic crustaceans, can be exposed to high metal levels, we studied the effects of in vitro exposure to Hg 2+ , Zn 2+ , Cu 2+ , and Cd 2+ on the activities of the proteasome from the claw muscles of lobsters (Homarus gammarus) and crabs (Cancer pagurus). The chymotrypsin like activity of the proteasome of these two species showed different sensitivity to metals. In lobsters the activity was significantly inhibited by all metals to a similar extent. In crabs the activities were severely suppressed only by Hg 2+ and Cu 2+ while Zn 2+ had only a moderate effect and Cd 2+ caused almost no inhibition of the crab proteasome. This indicates that the proteasomes of both species possess structural characteristics that determine different susceptibility to metals. Consequently, the proteasome-mediated protein degradation in crab C. pagurus may be less affected by metal pollution than that of the lobster H. gammarus.

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“…However, this phenomenon was not recognized in yeast cells that expressed the Cdc34 mutants. 6) These results suggest that the function of Cdc34 as a ubiquitin-conjugating enzyme is essential for resistance to MeHg.…”

Section: Reduction In Mehg Toxicity By Up System-mediated Acceleratiomentioning

confidence: 92%

Role of the Ubiquitin-proteasome System in Methylmercury Toxicity in Saccharomyces cerevisiae

Hwang

2011

JOURNAL OF HEALTH SCIENCE

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Methylmercury (MeHg) is an important environmental pollutant that causes severe disorders of the central nervous system, but the mechanism underlying its toxicity and the corresponding biological defense mechanisms remain largely unknown. Saccharomyces cerevisiae (S. cererisiae) yeast cells were used to elucidate the defense mechanisms against MeHg toxicity and to search for novel genes involved in MeHg resistance. S. cerevisiae is a eukaryotic organism that possesses many gene products that are functionally similar to those of mammals such as humans. We have previously reported that Cdc34 and Rad23 confer MeHg resistance to yeast cells. Interestingly, the both proteins are related to ubiquitin-proteasome system (UP system) that is involved in the intracellular degradation of proteins. In our detailed experiments, we found that the UP system might play an important role in lending protection against MeHg toxicity. This review summarizes the results of our studies on the role of the UP system as a defense mechanism against MeHg toxicity in yeast cells.

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Ubiquitin‐proteasome system is responsible for the protection of yeast and human cells against methylmercury

Cited by 49 publications

References 31 publications

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

The proteasomes of two marine decapod crustaceans, European lobster (Homarus gammarus) and Edible crab (Cancer pagurus), are differently impaired by heavy metals

Role of the Ubiquitin-proteasome System in Methylmercury Toxicity in Saccharomyces cerevisiae

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