Methylmercury chloride induces alveolar type II epithelial cell damage through an oxidative stress-related mitochondrial cell death pathway

Lu, Tien Hui; Chen, Chun Hung; Lee, Ming Jye; Ho, Tsung Jung; Leung, Yuk‐Man; Hung, Dong-Zong; Yen, Cheng Chien; He, Tsung Ying; Lin, Chen‐Yong

doi:10.1016/j.toxlet.2010.02.003

Cited by 39 publications

(11 citation statements)

References 43 publications

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“…Lu et al . reported that methylmercury chloride induces AECs‐II damage through an oxidative stress‐related mitochondrial cell death pathway . Our data showed that AECs‐II accumulation occurred during apoptosis in lung fibrosis and up‐regulation of miR‐30a could inhibit AECs‐II apoptosis.…”

Section: Discussionmentioning

confidence: 57%

MiRNA‐30a inhibits AECs‐II apoptosis by blocking mitochondrial fission dependent on Drp‐1

Mao

Zhang

Lin

et al. 2014

J Cellular Molecular Medi

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Apoptosis of type II alveolar epithelial cells (AECs-II) is a key determinant of initiation and progression of lung fibrosis. However, the mechanism of miR-30a participation in the regulation of AECs-II apoptosis is ambiguous. In this study, we investigated whether miR-30a could block AECs-II apoptosis by repressing mitochondrial fission dependent on dynamin-related protein-1 (Drp-1). The levels of miR-30a in vivo and in vitro were determined through quantitative real-time PCR (qRT-PCR). The inhibition of miR-30a in AECs-II apoptosis, mitochondrial fission and its dependence on Drp-1, and Drp-1 expression and translocation were detected using miR-30a mimic, inhibitor-transfection method (gain- and loss-of-function), or Drp-1 siRNA technology. Results showed that miR-30a decreased in lung fibrosis. Gain- and loss-of-function studies revealed that the up-regulation of miR-30a could decrease AECs-II apoptosis, inhibit mitochondrial fission, and reduce Drp-1 expression and translocation. MiR-30a mimic/inhibitor and Drp-1 siRNA co-transfection showed that miR-30a could inhibit the mitochondrial fission dependent on Drp-1. This study demonstrated that miR-30a inhibited AECs-II apoptosis by repressing the mitochondrial fission dependent on Drp-1, and could function as a novel therapeutic target for lung fibrosis.

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Section: Discussionmentioning

confidence: 57%

MiRNA‐30a inhibits AECs‐II apoptosis by blocking mitochondrial fission dependent on Drp‐1

Mao

Zhang

Lin

et al. 2014

J Cellular Molecular Medi

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“…Many factors, such as ionizing radiation, xenobiotics, and toxic metals can promote ROS generation, which triggers cell death and implicates in the development of various disorders [19,20]. Mercury induces toxic effects by causing oxidative stress from ROS production, which oxidizes the membrane lipids of cells and causes the alteration of cellular function, and eventually results in cell death and pathophysiological injuries in mammals [19–21,26]. Moreover, it has been reported that oxidative stress plays a crucial role in inducing pancreatic islet β-cell injuries and the pathogenesis of DM, probably as a result of excessive levels of mitochondrial ROS production and the presence of fewer antioxidant enzymes in pancreatic β-cells [29,30].…”

Section: Resultsmentioning

confidence: 99%

Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo

Chen

Liu

et al. 2012

IJMS

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Mercury is a toxic heavy metal that is an environmental and industrial pollutant throughout the world. Mercury exposure leads to many physiopathological injuries in mammals. However, the precise toxicological effects of mercury on pancreatic islets in vivo are still unclear. Here, we investigated whether mercuric compounds can induce dysfunction and damage in the pancreatic islets of mice, as well as the possible mechanisms involved in this process. Mice were treated with methyl mercuric chloride (MeHgCl, 2 mg/kg) and mercuric chloride (HgCl2, 5 mg/kg) for more than 2 consecutive weeks. Our results showed that the blood glucose levels increased and plasma insulin secretions decreased in the mice as a consequence of their exposure. A significant number of TUNEL-positive cells were revealed in the islets of mice that were treated with mercury for 2 consecutive weeks, which was accompanied by changes in the expression of the mRNA of anti-apoptotic (Bcl-2, Mcl-1, and Mdm-2) and apoptotic (p53, caspase-3, and caspase-7) genes. Moreover, plasma malondialdehyde (MDA) levels increased significantly in the mice after treatment with mercuric compounds for 2 consecutive weeks, and the generation of reactive oxygen species (ROS) in the pancreatic islets also markedly increased. In addition, the mRNA expression of genes related to antioxidation, including Nrf2, GPx, and NQO1, were also significantly reduced in these islets. These results indicate that oxidative stress injuries that are induced by mercuric compounds can cause pancreatic islets dysfunction and apoptosis in vivo.

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“…Markers of oxidative stress have been identified, demonstrating that aberrant antioxidant activity may exacerbate pulmonary fibrosis in patients and animal models ( 12 , 14 ). AEC II cells, which are known to be vulnerable to oxidative stress, produce and secrete the surfactant proteins (SPs), SP-A, SP-B, SP-C and SP-D (markers of alveolar epithelial cell function) in order to maintain morphological organization, biophysical functions, biochemical composition and immune function in lung tissue ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Conversion of bone marrow mesenchymal stem cells into type II alveolar epithelial cells reduces pulmonary fibrosis by decreasing oxidative stress in rats

Huang

Kang

Wang

et al. 2014

Molecular Medicine Reports

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Pulmonary fibrosis is an irreversible chronic progressive fibroproliferative lung disease, which usually has a poor prognosis. Previous studies have confirmed that the transplantation of bone marrow mesenchymal stem cells (MSCs) significantly reduces lung damage in a number of animal models. However, the underlying mechanism involved in this process remains to be elucidated. In the present study, a bleomycin (BLM)-induced female Wister rat model of fibrosis was established. At 0 or 7 days following BLM administration, rats were injected into the tail vein with 5-bromo-2-deoxyuridine-labeled MSCs extracted from male Wistar rats. The lung tissue of the rats injected with MSCs expressed the sex-determining region Y gene. The level surfactant protein C (SP-C), a marker for type II alveolar epithelial cells (AEC II), was higher in the group injected with MSCs at day 0 than that in the group injected at day 7. Furthermore, SP-C mRNA, but not aquaporin 5 mRNA, a marker for type I alveolar epithelial cells, was expressed in fresh bone marrow aspirates and the fifth generation of cultured MSCs. In addition, superoxide dismutase activity and total antioxidative capability, specific indicators of oxidative stress, were significantly increased in the lung tissue of the MSC-transplanted rats (P<0.05). In conclusion, to alleviate pulmonary fibrosis, exogenous MSCs may be transplanted into damaged lung tissue where they differentiate into AEC II and exert their effect, at least in part, through blocking oxidative stress.

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Methylmercury chloride induces alveolar type II epithelial cell damage through an oxidative stress-related mitochondrial cell death pathway

Cited by 39 publications

References 43 publications

MiRNA‐30a inhibits AECs‐II apoptosis by blocking mitochondrial fission dependent on Drp‐1

MiRNA‐30a inhibits AECs‐II apoptosis by blocking mitochondrial fission dependent on Drp‐1

Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo

Conversion of bone marrow mesenchymal stem cells into type II alveolar epithelial cells reduces pulmonary fibrosis by decreasing oxidative stress in rats

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