Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-regulated pathways

Lu, Tien-Hui; Tseng, To-Jung; Su, Chin-Chuan; Tang, Feng-Cheng; Yen, Chi-Hua; Liu, Yuyun; Yang, Ching-Yao; Wu, Chi‐Rei; Chen, Kuo-Liang; Hung, Dong-Zong; Chen, Yawen

doi:10.1016/j.toxlet.2013.10.013

Cited by 153 publications

(100 citation statements)

References 64 publications

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“…Toxic levels of arsenic in the blood interfere with many metabolic processes. Toxic arsenic induces oxidative stress through the generation of reactive oxygen species (ROS), leading to multi-system organ failure, chronic diseases and death [1]. Arsenic is ubiquitous and exists in multiple forms such as organic and inorganic compounds widely distributed in the environment to which man and animals are exposed.…”

Section: Introductionmentioning

confidence: 99%

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

et al. 2017

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(2017) Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway, Redox Report, 22:6, 467-477, DOI: 10.1080/13510002.2017 Objectives: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal. Methods: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal. Results: Exposure to arsenic caused a significant increase in malondialdehyde, H 2 O 2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the prosurvival protein-protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawal Discussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

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Section: Introductionmentioning

confidence: 99%

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

et al. 2017

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“…ii) increased APP expression and B amyloid formation [34], iii) impaired synaptic transmission [35], increased tau protein phosphorylation [36,37], and reticulum endoplasmic stress induction [38].…”

Section: Discussionmentioning

confidence: 99%

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

et al. 2016

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Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells.Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50 to 1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

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“…29) In addition, Lu et al recently reported that inorganic arsenic induces reactive oxygen species, causing neuronal cell death via both c-Jun N terminal kinase/extracellular signal-regulated kinase (JNK/ERK)-mediated mitochondria-dependent and GRP 78/CHOP-triggered apoptosis pathways. 30) These results indicate that exposure to inorganic arsenic at least contributes to neuronal cell death via a mitochondrial dependent pathway.…”

Section: Sodium Arsenite Induces Neural Cell Death Via a Mitochondriamentioning

confidence: 82%

Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage

Aung

Tsukahara

Maekawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Environmental influences, such as chemical exposure, have long been considered potential risk factors for neurodegenerative disorders, including neuromuscular diseases. However, no definitive links between environmental chemical exposure and a pathogenic mechanism of neurodegenerative disease has yet been established. In this study, we describe that exposure to arsenic, an environmental pollutant naturally found in drinking water, induces neuronal cell death and alteration of morphology, particularly neurite outgrowth and in the cytoskeleton of neurons. Since progressive cell loss accompanied by the alteration of neuronal structures and cytoskeleton is considered the major pathologic feature of neurodegenerative disorders, arsenic-induced neurotoxicity might contribute to an etiologic mechanism of some neurodegenerative diseases. Further, we discuss the importance of in vitro assay, particularly an embryonic toxicity test, for assessing the neurotoxicity of chemicals, because most of chemicals found in our environment remain to be evaluated regarding their neurotoxicity risk for neurodegenerative diseases.

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Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-regulated pathways

Cited by 153 publications

References 64 publications

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage

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