Pb 2+ modulates ryanodine receptors from the endoplasmic reticulum in rat brain

Jia, Qiyue; Du, Guihua; Yu, Li; Wang, Zhiping; Xie, Jie; Gu, Junwang; Yin, Guangming; Zhang, Shuyun; Gao, Yanyan; Zhou, Fankun; Feng, Chenglian; Fan, Guang

doi:10.1016/j.taap.2017.11.013

Cited by 16 publications

(4 citation statements)

References 57 publications

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“…Among heavy metals, lead easily crosses the blood-brain barrier and acts as an alternative to calcium ions, which leads to interference with the normal action of calcium ions in the brain [124], affecting the uptake, release, and binding of GABA in the rat brain [125], calcium release through ryanodine receptors, and calcium signaling, thereby causing neurotoxicity in the rat brain [126].…”

Section: Neurological Symptomsmentioning

confidence: 99%

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies

Koyama,

Kamogashira,

Yamasoba

2024

Antioxidants

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Heavy metals are often found in soil and can contaminate drinking water, posing a serious threat to human health. Molecular pathways and curation therapies for mitigating heavy metal toxicity have been studied for a long time. Recent studies on oxidative stress and aging have shown that the molecular foundation of cellular damage caused by heavy metals, namely, apoptosis, endoplasmic reticulum stress, and mitochondrial stress, share the same pathways as those involved in cellular senescence and aging. In recent aging studies, many types of heavy metal exposures have been used in both cellular and animal aging models. Chelation therapy is a traditional treatment for heavy metal toxicity. However, recently, various antioxidants have been found to be effective in treating heavy metal-induced damage, shifting the research focus to investigating the interplay between antioxidants and heavy metals. In this review, we introduce the molecular basis of heavy metal-induced cellular damage and its relationship with aging, summarize its clinical implications, and discuss antioxidants and other agents with protective effects against heavy metal damage.

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Section: Neurological Symptomsmentioning

confidence: 99%

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies

Koyama,

Kamogashira,

Yamasoba

2024

Antioxidants

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“…They are also associated with the activity-dependent structural plasticity of dendritic spines, neuronal cell death, hyperactive behaviours, and impaired learning and memory [66,67]. CACNA2D2 has been reported to be involved in methamphetamineinduced neurotoxicity [68], and RYRs in neurotoxicity induced by lead and 6-OHDA [69,70].…”

Section: Common Proteins Involved In Temperature-induced Neurotoxicitymentioning

confidence: 99%

The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Maffioli,

Nonnis,

Grassi Scalvini

et al. 2023

IJMS

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Neurotoxicity consists of the altered functionality of the nervous system caused by exposure to chemical agents or altered chemical–physical parameters. The neurotoxic effect can be evaluated from the molecular to the behavioural level. The zebrafish Danio rerio is a model organism used in many research fields, including ecotoxicology and neurotoxicology. Recent studies by our research group have demonstrated that the exposure of adult zebrafish to low (18 °C) or high (34 °C) temperatures alters their brain proteome and fish behaviour compared to control (26 °C). These results showed that thermal variation alters the functionality of the nervous system, suggesting a temperature-induced neurotoxic effect. To demonstrate that temperature variation can be counted among the factors that generate neurotoxicity, eight different protein datasets, previously published by our research group, were subjected to new analyses using an integrated proteomic approach by means of the Ingenuity Pathway Analysis (IPA) software (Release December 2022). The datasets consist of brain proteome analyses of wild type adult zebrafish kept at three different temperatures (18 °C, 26 °C, and 34 °C) for 4 days (acute) or 21 days (chronic treatment), and of BDNF+/− and BDNF−/− zebrafish kept at 26 °C or 34 °C for 21 days. The results (a) demonstrate that thermal alterations generate an effect that can be defined as neurotoxic (p value ≤ 0.05, activation Z score ≤ −2 or ≥2), (b) identify 16 proteins that can be used as hallmarks of the neurotoxic processes common to all the treatments applied and (c) provide three protein panels (p value ≤ 0.05) related to 18 °C, 34 °C, and BDNF depletion that can be linked to anxiety-like or boldness behaviour upon these treatments.

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“…At the top of The Agency for Toxic Substances and Disease Registry's priority list of hazardous substances are the metals arsenic (As), lead (Pb) and mercury (Hg), in that order based on their prevalence in the environment and threat to human health [10]. These metals all share the ability to cause neurotoxicity [11][12][13][14][15] and cause the most harm during development [16]. While a number of studies have addressed the effects of these metals individually and in various combinations, most have been observational and retrospective, lacking the control of a defined experimental model.…”

Section: Introductionmentioning

confidence: 99%

Developmental Toxicology of Metal Mixtures in Drosophila: Unique Properties of Potency and Interactions of Mercury Isoforms

Beamish

Love

Rand

2021

IJMS

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Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl2), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the Drosophila model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl2. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl2, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl2.

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Pb 2+ modulates ryanodine receptors from the endoplasmic reticulum in rat brain

Cited by 16 publications

References 57 publications

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies

The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Developmental Toxicology of Metal Mixtures in Drosophila: Unique Properties of Potency and Interactions of Mercury Isoforms

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