MeHg-induced autophagy via JNK/Vps34 complex pathway promotes autophagosome accumulation and neuronal cell death

Lin, Tao; Ruan, Shijuan; Huang, Dingbang; Meng, Xiang‐Jin; Li, Wenjun; Wang, Bin; Zou, Fei

doi:10.1038/s41419-019-1632-z

Cited by 41 publications

(11 citation statements)

References 59 publications

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“…Once the active ULK complex is recruited to the initiation site, autophagy proceeds to the next stage, i.e., the formation of autophagosomes. It has been shown that the Beclin1-VPS34-Atg14L complex is critical to the formation of autophagosomes [84]. Activated ULK1 phosphorylates Beclin1 at Ser15 and ATG14 at Ser29.…”

Section: The Canonical Role Of Ulk1mentioning

confidence: 99%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.

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Section: The Canonical Role Of Ulk1mentioning

confidence: 99%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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“…One possible explanation for this finding could be that exposure to MeHg-Cys inhibits or causes degradation of the autophagic machinery. Some previous studies, using in vitro and in vivo models, reported a reduction in autophagy following exposure to MeHg [ 43 , 44 ], while other studies have shown that exposure to low doses of MeHg enhances autophagy [ 45 ]. These reported differences may be due to variations among the cell types studied, differences in the concentrations of MeHg used for the study, and the exposure time for each study.…”

Section: Discussionmentioning

confidence: 99%

Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Ganapathy

Farrell

Vaghela

et al. 2021

IJMS

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Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.

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“…MeHg affected lysosomal permeability as well. All of which resulted in MeHg induced cell death [ 67 ].…”

Section: Methodsmentioning

confidence: 99%

Role of neurotoxicants in the pathogenesis of Alzheimer’s disease: a mechanistic insight

et al. 2021

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Alzheimer’s disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis. Key messages Inevitable cascade mechanisms of how Alzheimer’s Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed. Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited. Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.

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MeHg-induced autophagy via JNK/Vps34 complex pathway promotes autophagosome accumulation and neuronal cell death

Cited by 41 publications

References 59 publications

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Role of neurotoxicants in the pathogenesis of Alzheimer’s disease: a mechanistic insight

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