NADPH oxidase regulates paraquat and maneb-induced dopaminergic neurodegeneration through ferroptosis

Hou, Liyan; Huang, Ruixue; Sun, Fuqiang; Zhang, Lin; Wang, Qingshan

doi:10.1016/j.tox.2019.02.011

Cited by 81 publications

(65 citation statements)

References 54 publications

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“…Herein, we discovered that ACADSB negatively regulated the expressions of GSR and GPX4 in SW620 cells. MDA is a final product of lipid peroxidation, which can lead to cell injury via cross-linking and polymerization of life molecules, such as proteins and nucleic acids (Hou, Huang, Sun, Zhang, & Wang, 2019). In the current research, it was uncovered that ACADSB overexpression notably enhanced the concentrations of MDA, Fe + , and lipid peroxidation in SW620 cells, but reduced the concentration of GSH.…”

Section: Discussionmentioning

confidence: 99%

ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Lü

Yang

Qing

et al. 2020

Cell Biology International

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Colorectal cancer (CRC) is one of the most pressing health issues in today's society. As such, it is imperative that the scientific community devise effective methods to inhibit the proliferation and metastasis of CRC cells. Ferroptosis is a recently discovered regulatory cell death mode mainly manifested by dysregulation of cellular iron metabolism and mitochondrial lipid peroxidation. ACADSB is a member of the acyl-CoA dehydrogenase. This study finds that ACADSB is lowly expressed in CRC tissues. Its expression is negatively correlated with N-and M-stage CRC but positively correlated with the overall survival rate of CRC patients. In addition, it finds that ACADSB is found in the mitochondria of cells. Overexpression of ACADSB inhibits CRC cell migration, invasion, and proliferation, while ACADSB knockdown has the opposite effect. More importantly, the study finds that ACADSB negatively regulates expression of glutathione reductase and glutathione peroxidase 4, the two main enzymes responsible for clearing glutathione (GSH) in CRC cells. ACADSB overexpression enhances the concentration of malondialdehyde, Fe + , superoxide dismutase, and lipid peroxidation in CRC cells, but reduces the concentration of GSH. This is significant, as all of these are important indicators of ferroptosis. Evaluating the data as a whole, this paper speculates that ACADSB affects CRC cell migration, invasion, and proliferation by regulating CRC cell ferroptosis.

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Section: Discussionmentioning

confidence: 99%

ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Lü

Yang

Qing

et al. 2020

Cell Biology International

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“…Studies have found that the 4-hydroxy-2-non-enal (4-HNE) adduct (a lipid peroxidation marker) in the caudate and putamen of HD brain and the striatum of HD mice was increased (Lee et al, 2011). And in the study of the damage of dopaminergic neurons by paraquat and mancozeb, it was found that NADPH oxidase activation caused lipid peroxidation, which led to ferroptosis in SH-SY5Y cells (Hou et al, 2019). Besides, the rupture of the vessel wall in hemorrhagic stroke results in the accumulation and dissolution of iron-rich erythrocytes in the brain parenchyma and subsequent excessive presence of hemoglobin and heme iron in the extracellular environment, resulting in iron-induced lipid peroxidation and ferroptosis (DeGregorio-Rocasolano et al, 2019).…”

Section: Ferroptosis In Other Neurodegenerative Diseasesmentioning

confidence: 99%

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

2020

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“…The pro-inflammatory cytokines in SGZ and SVZ, including IL-6, IL-1β, TNF-α, were significantly increased in mice treated with 20 mg/kg PQ, indicating that the neuroinflammation indeed occurred. Previously, others and we reported that PQ-induced damages of brain function were associated with neuroinflammation, increased ROS and mitochondrial dysfunction 14,[38][39][40] . Upon environmental stresses, neuroinflammation could be induced by microglia and/ or astrocytes which were regarded as the main pro-inflammatory cytokines secreting cells in the brain 28 .…”

Section: Discussionmentioning

confidence: 71%

“…Actually, as most primordial cell in the central nervous system, the NSC appeared to promote function preservation and/or restoration in neurodegenerative disease 12 . Besides, PQ-induced functional impairments in progenitor cell in vitro were also reported [13][14][15] . However, to date, there is no study evaluating the direct toxicity of PQ to NSC in vivo.…”

mentioning

confidence: 92%

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat

Yang

Shao

Zhao

et al. 2020

Sci Rep

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Paraquat (PQ), a widely used herbicide, could cause neurodegenerative diseases, yet the mechanism remains incompletely understood. This study aimed to investigate the direct effect of PQ on NSC in vivo and its possible mechanism. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control once a week for 2 weeks, and sacrificed 1 week after the last PQ injection. Furthermore, extra experiments with Tauroursodeoxycholic Acid (TUDCA) intervention were performed to observe the relationship between ER stress, neuroinflammation and the neural stem cell (NSC) impairment. The results showed that 20 mg/kg PQ caused the NSC number decrease in both subgranular zones (SGZ) and subventricular zone (SVZ). Further analysis indicated that the 20 mg/kg PQ suppressed the proliferation of NSC, without affecting the apoptosis. Moreover, 20 mg/kg PQ also induced ER stress in microglia and caused neuroinflammation in SGZ and SVZ. Interestingly, the ER stress inhibitor could simultaneously ameliorate the neuroinflammation and NSC reduction. These data suggested that increased ER stress in microglia might be a possible pathway for PQ-induced neuroinflammation and NSC impairment. That is a previously unknown mechanism for PQ neurotoxicity.

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NADPH oxidase regulates paraquat and maneb-induced dopaminergic neurodegeneration through ferroptosis

Cited by 81 publications

References 54 publications

ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat

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