Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity

Zhang, Xinglai; Yang, Hongmei; Wang, Yi; Zhang, Jun; Zhang, Huajie; Cao, Xueshan; Hu, Ting; Lin, Jing; Tang, Xiaoxiao; Yan, Xi; Zhuang, Hongbing; Chen, Xiaolu; Liang, Yuxuan; Luo, Peng; Shen, Liming

doi:10.1021/acschemneuro.3c00009

Cited by 8 publications

(3 citation statements)

References 98 publications

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“…In our recent proteomic analysis, we identified an extensive array of proteins associated with mitochondrial functionality, oxidative stress, the ubiquitin–proteasome system (UPS), and endoplasmic reticulum (ER) stress, as well as processes related to translation, transcription, and nuclear transport. Numerous studies have identified mitochondrial dysfunction as a key factor associated with the onset of oxidative stress, which is a pivotal event in chemical-induced neurotoxicity and developmental neurotoxicity induced by arsenic exposure ( Medda et al, 2020 ; Zhang et al, 2023 ). Notably, the exposure of NPCs to NA has exhibited marked neurotoxicity, characterized by the generation of reactive oxygen species (ROS), upregulated expression of HO-1, and the enhanced presence of antioxidant proteins, such as PDXK, GSTM3, and NDUFA10.…”

Section: Discussionmentioning

confidence: 99%

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A protein–miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Jahan,

Ansari,

Srivastava

et al. 2024

Front. Pharmacol.

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Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood–brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

“…Nobiletin displays a wide range of beneficial effects against the features of NDs. However, further studies are needed to determine its primary molecular targets using proteomic-based approaches ( Zhang et al, 2013 ; Braidy et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

A protein–miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Jahan,

Ansari,

Srivastava

et al. 2024

Front. Pharmacol.

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“…Other compounds, such as ellagic acid, resveratrol, rutin, and taurine, deserve a separate mention, since, in addition to the neuroprotective effects mentioned above, they also ameliorate As-induced cognitive and behavioral impairments in in vivo rodent models [193,204,206,289]. Recently, Dictyophora polysaccharide, a bioactive compound from medicinal and edible fungus, has been used as a tool against As neurotoxicity due its anti-inflammatory and immunomodulatory activities [290,291].…”

Section: Nutritional Interventions and Natural Compoundsmentioning

confidence: 99%

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure

Vázquez Cervantes,

González Esquivel,

Ramírez Ortega

et al. 2023

Cells

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Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and for medical applications; its industrial use has recently decreased or has been discontinued due to its toxicity. Due to its versatile applications and distribution, there is a wide spectrum of human As exposure sources, mainly contaminated drinking water. The fact that As is present in drinking water implies chronic human exposure to this metalloid; it has become a worldwide health problem, since over 200 million people live where As levels exceed safe ranges. Many health problems have been associated with As chronic exposure including cancer, cardiovascular diseases, gastrointestinal disturbances, and brain dysfunctions. Because As can cross the blood–brain barrier (BBB), the brain represents a target organ where this metalloid can exert its long-term toxic effects. Many mechanisms of As neurotoxicity have been described: oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction; all of them can converge, thus leading to impaired cellular functions, cell death, and in consequence, long-term detrimental effects. Here, we provide a current overview of As toxicity and integrated the global mechanisms involved in cognitive and behavioral impairment induced by As exposure show experimental strategies against its neurotoxicity.

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Effects of arsenic exposure on blood trace element levels in rats and sex differences

Ran,

Yan,

Zhuang

et al. 2024

Biometals

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Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity

Cited by 8 publications

References 98 publications

A protein–miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

A protein–miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure

Effects of arsenic exposure on blood trace element levels in rats and sex differences

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