PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells

Zhang, Hongtao; Mi, Lan; Wang, Ting; Yuan, Lamei; Li, Xuehui; Dong, Lixin; Zhao, Peng; Fu, Junjie; Yao, Biyun; Zhou, Zhenming

doi:10.1016/j.tiv.2016.04.006

Cited by 59 publications

(39 citation statements)

References 64 publications

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“…PINK1 is the kinase that could phosphorylate and activate parkin in the process of damaged mitochondria clearance by autophagy, which exerts neuroprotection against ROS overproduction [ 18 ]. It was reported that loss of PINK1 or parkin induced mitochondrial dysfunction and consequent overproduction of ROS, while overexpression of PINK1 or parkin protected against ROS-induced cell death [ 19 , 20 ]. Parkin is an E3 ubiquitin ligase, and loss of function leads to autosomal recessive PD [ 21 ].…”

Section: Ros and Pd-associated Factorsmentioning

confidence: 99%

The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

Weng

Xie

Liu

et al. 2018

Parkinson's Disease

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Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. The precise mechanism underlying pathogenesis of PD is not fully understood, but it has been widely accepted that excessive reactive oxygen species (ROS) are the key mediator of PD pathogenesis. The causative factors of PD such as gene mutation, neuroinflammation, and iron accumulation all could induce ROS generation, and the later would mediate the dopaminergic neuron death by causing oxidation protein, lipids, and other macromolecules in the cells. Obviously, it is of mechanistic and therapeutic significance to understand where ROS are derived and how ROS induce dopaminergic neuron damage. In the present review, we try to summarize and discuss the main source of ROS in PD and the key pathways through which ROS mediate DA neuron death.

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Section: Ros and Pd-associated Factorsmentioning

confidence: 99%

The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

Weng

Xie

Liu

et al. 2018

Parkinson's Disease

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“…Recent research has revealed that environmental factor-induced cellular aging and mitochondriopathies have been linked to inhibition of mitophagy, which would exert huge influence on cellular stability. 50 Caspase 1-mediated cell death can be partially recovered through mitophagy. On the contrary, inhibition of mitophagy may further deteriorate cellular function, confirming the positive role of mitophagy.…”

Section: Autophagymentioning

confidence: 99%

Dysfunction of various organelles provokes multiple cell death after quantum dot exposure

Wang

Tang

2018

IJN

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Quantum dots (QDs) are different from the materials with the micrometer scale. Owing to the superiority in fluorescence and optical stability, QDs act as possible diagnostic and therapeutic tools for application in biomedical field. However, potential threats of QDs to human health hamper their wide utilization in life sciences. It has been reported that oxidative stress and inflammation are involved in toxicity caused by QDs. Recently, accumulating research unveiled that disturbance of subcellular structures plays a magnificent role in cytotoxicity of QDs. Diverse organelles would collapse during QD treatment, including DNA damage, endoplasmic reticulum stress, mitochondrial dysfunction and lysosomal rupture. Different forms of cellular end points on the basis of recent research have been concluded. Apart from apoptosis and autophagy, a new form of cell death termed pyroptosis, which is finely orchestrated by inflammasome complex and gasdermin family with secretion of interleukin-1 beta and interleukin-18, was also summarized. Finally, several potential cellular signaling pathways were also listed. Activation of Toll-like receptor-4/myeloid differentiation primary response 88, nuclear factor kappa-light-chain-enhancer of activated B cells and NACHT, LRR and PYD domains-containing protein 3 inflammasome pathways by QD exposure is associated with regulation of cellular processes. With the development of QDs, toxicity evaluation is far behind its development, where specific mechanisms of toxic effects are not clearly defined. Further studies concerned with this promising area are urgently required.

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“…Although cell models cannot recapitulate in vivo cellular responses in brain, several studies show the utility of human neuroblastoma SH-SY5Y cells for study of mitochondrial dysfunction, such as that caused by environmental toxicants, Mn, and pesticides (de Oliveira et al, 2017;Fernandes et al, 2017;Oh et al, 2016;Wang et al, 2014;Zhang et al, 2016). In a previous study, we calibrated cellular Mn contents in SH-SY5Y cells to achieve values comparable to those in human brain and found that Mn-stimulated mitochondrial respiration and H 2 O 2 production in dose-dependent manners (Fernandes et al, 2017).…”

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confidence: 99%

Metabolomic Responses to Manganese Dose in SH-SY5Y Human Neuroblastoma Cells

Fernandes

Chandler

Liu

et al. 2019

Toxicological Sciences

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Manganese (Mn)-associated neurotoxicity has been well recognized. However, Mn is also an essential nutrient to maintain physiological function. Our previous study of human neuroblastoma SH-SY5Y cells showed that Mn treatment comparable to physiological and toxicological concentrations in human brain resulted in different mitochondrial responses, yet cellular metabolic responses associated with such different outcomes remain uncharacterized. Herein, SH-SY5Y cells were examined for metabolic responses discriminated by physiological and toxicological levels of Mn using high-resolution metabolomics (HRM). Before performing HRM, we examined Mn dose (from 0 to100 lM) and time effects on cell death. Although we did not observe any immediate cell death after 5 h exposure to any of the Mn concentrations assessed (0-100 lM), cell loss was present after a 24-h recovery period in cultures treated with Mn ! 50 lM. Exposure to Mn for 5 h resulted in a wide range of changes in cellular metabolism including amino acids (AA), neurotransmitters, energy, and fatty acids metabolism. Adaptive responses at 10 lM showed increases in neuroprotective AA metabolites (creatine, phosphocreatine, phosphoserine). A 5-h exposure to 100 mM Mn, a time before any cell death occurred, resulted in decreases in energy and fatty acid metabolites (hexose-1,6 bisphosphate, acyl carnitines). The results show that adjustments in AA metabolism occur in response to Mn that does not cause cell death while disruption in energy and fatty acid metabolism occur in response to Mn that results in subsequent cell death. The present study establishes utility for metabolomics analyses to discriminate adaptive and toxic molecular responses in a human in vitro cellular model that could be exploited in evaluation of Mn toxicity.

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PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells

Cited by 59 publications

References 64 publications

The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

Dysfunction of various organelles provokes multiple cell death after quantum dot exposure

Metabolomic Responses to Manganese Dose in SH-SY5Y Human Neuroblastoma Cells

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