Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway

Yen, Yuan-Peng; Tsai, Keh–Sung; Chen, Yawen; Huang, Chun-Fa; Yang, Rong‐Sen; Liu, Shing‐Hwa

doi:10.1007/s00204-012-0864-9

Cited by 147 publications

(87 citation statements)

References 64 publications

(66 reference statements)

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“…The SMase-p47phox-ROS cascade has been described in vascular smooth muscle cells under hypoxia conditions (8) and in neurons exposed to TNF-alpha (4), however, to the best of our knowledge, the relationship of this cascade with ER stress has never been studied. Furthermore, several studies showed that cellular toxics such as arsenic or ischemia/reperfusion injury exert their cytotoxicity by inducing apoptosis through a ROS-induced ER stress which is associated to a mitochondrial dysfunction (29,34). In the present study, we provide evidence that mitochondrial ROS increase, changes on mitochondrial respiration and complex IV activity are detected at late (24 hours) but not early (4 hours) MP treatment, and are abolished when ER stress is inhibited, indicating that ER stress activation is mandatory for the generation of mitochondrial ROS and perturbation of mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction

SafiedeenZainab

Rodríguez-Gómez

VergoriLuisa

et al. 2017

Antioxidants & Redox Signaling

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Aims: Circulating microparticles (MPs) from metabolic syndrome patients and those generated from apoptotic T-cells induce endothelial dysfunction; however, the molecular and cellular mechanism(s) underlying in the effects of MPs remain to be elucidated. Results: Here, we show that both types of MPs increased expression of endoplasmic reticulum (ER) stress markers XBP-1, p-eIF2alpha and CHOP and nuclear translocation of ATF6 on human aortic endothelial cells. MPs decreased in vitro nitric oxide release by human aortic endothelial cells, whereas in vivo MP injection into mice impaired the endothelium-dependent relaxation induced by acetylcholine. These effects were prevented when ER stress was inhibited suggesting that ER stress is implicated in the endothelial effects induced by MPs. MPs affected mitochondrial function and evoked sequential increase of cytosolic and mitochondrial reactive oxygen species (ROS). Pharmacological inhibition of ER stress and silencing of neutral sphingomyelinase with siRNA abrogated all MP-mediated effects. Neutralization of Fas-Ligand carried by MPs abolished effects induced by both MP types, whereas neutralization of low density lipoprotein-receptor on endothelial cells prevented T-lymphocyte MP-mediated effects. Innovation and Conclusion: Collectively, endothelial dysfunction triggered by MPs involves temporal cross-talk between ER and mitochondria with respect to spatial regulation of ROS via the neutral sphingomyelinase and interaction of MPs with Fas and/or low density lipoprotein-receptor. These results provide a novel molecular insight into the manner MPs mediate vascular dysfunction and allow identification of potential therapeutic targets to treat vascular complications associated with metabolic syndrome.

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Section: Discussionmentioning

confidence: 99%

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction

SafiedeenZainab

Rodríguez-Gómez

VergoriLuisa

et al. 2017

Antioxidants & Redox Signaling

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“…A previous report proposed that arsenite exerts its cytotoxic effect on myoblasts by inducing apoptosis, evidenced by reactive oxygen species (ROS)-induced mitochondrial dysfunction, endoplasmic reticulum stress, and Akt inactivation signaling pathway [66]. Also, arsenite was found to induce apoptosis in lymphoblastic cells [67].…”

Section: Discussionmentioning

confidence: 99%

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway

Gonzalez

Lema

Kirken

et al. 2015

CCAND

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Long-term exposure to arsenic has been linked to cancer in different organs and tissues, including skin. Here, non-malignant human keratinocytes (HaCaT) were exposed to arsenic and its effects on microRNAs (miRNAs; miR) expression were analyzed via miRCURY LNA array analyses. A total of 30 miRNAs were found differentially expressed in arsenic-treated cells, as compared to untreated controls. Among the up-regulated miRNAs, miR-21, miR-200a and miR-141, are well known to be involved in carcinogenesis. Additional findings confirmed that those three miRNAs were indeed up-regulated in arsenic-stimulated keratinocytes as demonstrated by quantitative PCR assay. Furthermore, bioinformatics analysis of both potential cancer-related pathways and targeted genes affected by miR-21, miR-200a and/or miR-141 was performed. Results revealed that miR-21, miR-200a and miR-141 are implicated in skin carcinogenesis related with melanoma development. Conclusively, our results indicate that arsenic-treated keratinocytes exhibited alteration in the miRNAs expression profile and that miR-21, miR-200a and miR-141 could be promising early biomarkers of the epithelial phenotype of cancer cells and they could be potential novel targets for melanoma therapeutic interventions.

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“…Consequently, disruption of mitochondrial metabolism not only resulted in failure of energy production, but also an increase in intracellular reactive oxygen species (ROS). In addition, As caused oxidative modification of proteins such as nitrosylation in the brain of As-treated rats and induced ER stress as well as disturbed homeostasis of intracellular calcium, which caused neuronal dysfunction and death (Florea et al 2007;Fan et al 2010;Yen et al 2012). Overall, it is noteworthy to concern that the complicated crosstalking between mitochondria, ER, and oxidative stress may synergistically augment the As-induced neurotoxicity (Brookes et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Taurine resumed neuronal differentiation in arsenite-treated N2a cells through reducing oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction

et al. 2014

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The goal of the study is to investigate the preventive effect of taurine against arsenite-induced arrest of neuronal differentiation in N2a cells. Our results revealed that taurine reinstated the neurite outgrowth in arsenite-treated N2a cells. Meanwhile, arsenite-induced oxidative stress and mitochondrial dysfunction as well as degradation of mitochondria DNA (mtDNA) were also inhibited by co-treatment of taurine. Since oxidative stress and mitochondrial dysfunction is closely associated with endoplasmic reticulum (ER) stress, we further examined indicators of ER stress, 78 kDa glucose-regulated protein (GRP78), and C/EBP-homologous protein (CHOP) protein expression. The results demonstrated that taurine significantly reduced arsenite-induced ER stress in N2a cells. In the parallel experiment, arsenite-induced disruption of intracellular calcium homeostasis was also ameliorated by taurine. The proven bio-function of taurine preserved a preventive effect against deleteriously cross-talking between oxidative stress, mitochondria, and ER. Overall, the results of the study suggested that taurine reinstated neuronal differentiation by inhibiting oxidative stress, ER stress, and mitochondrial dysfunction in arsenite-treated N2a cells.

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Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway

Cited by 147 publications

References 64 publications

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway

Taurine resumed neuronal differentiation in arsenite-treated N2a cells through reducing oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction

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