Biological Effects of and Responses to Exposure to Electrophilic Environmental Chemicals

Sumi, Daigo

doi:10.1248/jhs.54.267

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…Taking into account these observations, it is reasonable to assume that nucleophilic groups other than GSH’s thiol could be more reactive toward MeHg, allowing for the formation of high affinity complexes, thus leading to dysfunction of important cellular molecules with nucleophilic properties. In agreement with this hypothesis, thiol groups from specific proteins [tyrosine phosphatase (Sumi, 2008) and creatine kinase (Wang et al, 2001)] are more nucleophilic and, consequently, more reactive than GSH (Farina et al, 2010). Toxicological consequences of this phenomenon have already been reported (Glasser et al, 2010).…”

Section: Mehg Interacts With Selenol Groupsmentioning

confidence: 75%

Mechanisms of methylmercury-induced neurotoxicity: Evidence from experimental studies

2011

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Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle.

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Section: Mehg Interacts With Selenol Groupsmentioning

confidence: 75%

Mechanisms of methylmercury-induced neurotoxicity: Evidence from experimental studies

2011

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“…), as well as with nonprotein thiols (i.e. glutathione, cysteine), are crucial events in mediating its neurotoxicity (Clarkson et al, 2003; Sumi, 2008). By direct interaction with thiols, as well as indirect mechanisms (discussed latter), MeHg can modify the oxidation state of the -SH groups on proteins, modulating their functions (Kim et al, 2002).…”

Section: Mercurymentioning

confidence: 99%

Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury

Farina

Ávila

Rocha

et al. 2013

Neurochemistry International

470

266

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Essential metals are crucial for the maintenance of cell homeostasis. Among the 23 elements that have known physiological functions in humans, 12 are metals, including iron (Fe) and manganese (Mn). Nevertheless, excessive exposure to these metals may lead to pathological conditions, including neurodegeneration. Similarly, exposure to metals that do not have known biological functions, such as mercury (Hg), also present great health concerns. This reviews focuses on the neurodegenerative mechanisms and effects of Fe, Mn and Hg. Oxidative stress (OS), particularly in mitochondria, is a common feature of Fe, Mn and Hg toxicity. However, the primary molecular targets triggering OS are distinct. Free cationic iron is a potent pro-oxidant and can initiate a set of reactions that form extremely reactive products, such as OH•. Mn can oxidize dopamine (DA), generating reactive species and also affect mitochondrial function, leading to accumulation of metabolites and culminating with OS. Cationic Hg forms have strong affinity for nucleophiles, such as –SH and –SeH. Therefore, they target critical thiol- and selenol-molecules with antioxidant properties. Finally, we address the main sources of exposure to these metals, their transport mechanisms into the brain, and therapeutic modalities to mitigate their neurotoxic effects.

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“…Cys is known to be a strong nucleophile within various proteins, although its nucleophilicity depends on the pH and on the immediate area surrounding the amino acid residue. 43 To confirm the covalent bond formation between β-Lg and shikonin, a tryptic digest of β-LgA and β-LgA−SHI was performed, and the two resulting peptide maps, which were obtained by means of HPLC-MS analysis, were compared.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Addition of β-Lactoglobulin Produces Water-Soluble Shikonin

Albreht

Vovk

Simonovska

2012

J. Agric. Food Chem.

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Shikonin and its ester derivatives belong to a group of secondary metabolites with a wide array of beneficial effects on human health. However, shikonin is principally used in oil-based preparations due to the low solubility of the pigment in aqueous media, and the positive properties of shikonin are not exploited to their full potential. Such low aqueous solubility often results in poor bioavailability, makes shikonin undesirable for oral administration, and restricts its broadened use in the food and pharmaceutical industries. The purpose of this study was to enhance the aqueous solubility of shikonin by the addition of β-lactoglobulin and to characterize the macromolecule-ligand binding interaction by means of spectrophotometry, spectrofluorometry, high-performance liquid chromatography, and mass spectrometry. In the presence of β-lactoglobulin the solubility of shikonin is increased up to 181-fold. One shikonin molecule binds covalently to β-lactoglobulin via Cys(121), whereas the remaining pigment molecules most probably bind to the protein via noncovalent interactions.

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Biological Effects of and Responses to Exposure to Electrophilic Environmental Chemicals

Cited by 17 publications

References 34 publications

Mechanisms of methylmercury-induced neurotoxicity: Evidence from experimental studies

Mechanisms of methylmercury-induced neurotoxicity: Evidence from experimental studies

Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury

Addition of β-Lactoglobulin Produces Water-Soluble Shikonin

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