Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate

Kharroubi, Wafa; Ahmed, Samia Haj; Nury, Thomas; Andreoletti, Pierre; Sakly, R; Hammami, Mohamed; Lizard, Gérard

doi:10.1016/j.jes.2016.08.028

Cited by 22 publications

(13 citation statements)

References 30 publications

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“…These include genes encoding subunits of Complex I (NADH: ubiquinone oxidoreductase) -Ndufa5, Ndufa8, Ndufa12, Ndufc1, Ndufv1; Complex III (cytochrome bc1 complex) -Uqcrc1; Complex IV (cytochrome c oxidase) -Cox7c, Cox8c, Cox15; and, complex V (ATP synthase) -ATP5a1. These findings are in broad agreement with a recent study that observed decreases in the activities of various mitochondrial complexes (I, II and IV) in microglial cells exposed to arsenate [76]. Altered expression of these genes support the premise that mitochondria are one of the major targets of arsenate's toxicity in CNCCs and that key mitochondrial processes (including ETC/oxidative phosphorylation) are adversely impacted.…”

Section: Mitochondrial Functionsupporting

confidence: 92%

“…The uncoupling mechanism is attributed to the highly unstable arsenate-phosphate ester that is rapidly hydrolyzed leading to a deficit in ATP production and conservation [72,75]. Moreover, perturbation of the mitochondrial ETC increases ROS levels that can also inhibit aerobic respiration, alter membrane potential and reduce ATP levels [76,77]. Not surprisingly, mitochondrial components, including enzymes involved in ETC/oxidative phosphorylation represent a significantly affected category of genes whose expression is altered in CNCCs in response to maternal arsenate exposure ( Supplementary Table 3E).…”

Section: Mitochondrial Functionmentioning

confidence: 99%

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Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

Mukhopadhyay

Seelan

Greene

et al. 2019

Reproductive Toxicology

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Prenatal exposure to arsenic, a naturally occurring toxic element, causes neural tube defects (NTDs) and, in animal models, orofacial anomalies. Since aberrant development or migration of cranial neural crest cells (CNCCs) can also cause similar anomalies within developing embryos, we examined the effects of in utero exposure to sodium arsenate on gene expression patterns in pure populations of CNCCs, isolated by fluorescence activated cell sorting (FACS), from Cre/ LoxP reporter mice. Changes in gene expression were analyzed using Affymetrix GeneChip ® microarrays and expression of selected genes was verified by TaqMan quantitative real-time PCR. We report, for the first time, arsenate-induced alterations in the expression of a number of novel candidate genes and canonical cascades that may contribute to the pathogenesis of orofacial defects. Ingenuity Pathway and NIH-DAVID analyses revealed cellular response pathways, biological themes, and potential upstream regulators, that may underlie altered fetal programming of arsenate exposed CNCCs.

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Section: Mitochondrial Functionsupporting

confidence: 92%

Section: Mitochondrial Functionmentioning

confidence: 99%

Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

Mukhopadhyay

Seelan

Greene

et al. 2019

Reproductive Toxicology

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“…The electron leakage of the mitochondrial electron transport chain is one of the main sources of ROS, which are usually generated from the mitochondrial dysfunction 51,52. Mitochondrial MP is essential to maintain the normal mitochondrial function, whose decrease leads to the defects to the insufficient synthesis of adenosine triphosphate (ATP) 53. ATP is produced in the mitochondrial inner membrane during the biological oxidation process.…”

Section: Discussionmentioning

confidence: 99%

<p>Regulating intracellular ROS signal by a dual pH/reducing-responsive nanogels system promotes tumor cell apoptosis</p>

Dong¹,

Lei²,

Guo³

et al. 2019

IJN

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Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly ( N -isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, P ss NCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells. Methods: The P ss NCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells. Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels. Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.

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“…It inhibits the mitochondrial complexes I, II, and IV of the electron transport chain, which increases ROS. As microglia is sensitive to arsenic toxicity [As (III)], the mitochondrial disturbance may induce apoptosis in microglial cells [160,161]. Arsenic has shown to induce alterations in the arachidonic acid metabolism and induces neuronal damage and inflammatory response in mice [162].…”

Section: Arsenic (As)mentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

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Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

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Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate

Cited by 22 publications

References 30 publications

Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

<p>Regulating intracellular ROS signal by a dual pH/reducing-responsive nanogels system promotes tumor cell apoptosis</p>

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

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