Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway

Seo, Jong Bae; Jung, Seung Ryoung; Hille, Bertil; Koh, Duk Su

doi:10.1007/s10565-016-9331-3

Cited by 16 publications

(6 citation statements)

References 60 publications

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“…It is interesting that P2y 2 expression is maintained at levels comparable to freshly isolated AIDUCs. While P2Y 2 receptors have been implicated in the pathogenesis of diseases and inflammation 62 , up-regulation of the receptor has been shown to confer protection in tissues under oxidative stress conditions 63 , 64 . Studies of mouse SMG cells cultured in vitro report up-regulation of P2y 2 , which is important for migration, aggregation, and self-organization 59 .…”

Section: Resultsmentioning

confidence: 99%

Development of a functional salivary gland tissue chip with potential for high-content drug screening

et al. 2021

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Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

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Section: Resultsmentioning

confidence: 99%

Development of a functional salivary gland tissue chip with potential for high-content drug screening

et al. 2021

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“…Multiple mechanisms were involved in the neuroprotective effects of extracellular ATP. For instance, extracellular ATP binding to P2Y1 receptors protected pancreatic duct epithelial cells via cAMP signaling pathway [53]. Extracellular ATP binding to P2Y13 purinergic receptors could neuroprotect astrocytes via PI3K/Akt/GSK3 pathway [54].…”

Section: Discussionmentioning

confidence: 99%

Extracellular ATP Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

Xiong

Zhou

Zheng

et al. 2022

Preprint

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Glutamate-induced neuroexcitotoxicity causes neuronal death in neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting NMDA receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity via binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular ROS overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity via Erk1/2-mediated autophagy inhibition, implying the promising potential of ATP for the treatment of neurodegenerative disorders.

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“…Multiple mechanisms were involved in the neuroprotective effects of extracellular ATP. For instance, extracellular ATP binding to P2Y1 receptors protected pancreatic duct epithelial cells via cAMP signaling pathway ( Seo et al, 2016 ). Extracellular ATP binding to P2Y13 purinergic receptors could neuroprotect astrocytes via PI3K/Akt/GSK3 pathway ( Carrasquero et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Adenosine Triphosphate Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

et al. 2022

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Glutamate-induced neuroexcitotoxicity could be related to the pathophysiology of some neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting N-Methyl-D-Aspartate (NMDA) receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity via binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular reactive oxygen species (ROS) overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity via Erk1/2-mediated autophagy inhibition, implying the potential of ATP for the treatment of neurodegenerative disorders.

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Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway

Cited by 16 publications

References 60 publications

Development of a functional salivary gland tissue chip with potential for high-content drug screening

Development of a functional salivary gland tissue chip with potential for high-content drug screening

Extracellular ATP Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

Extracellular Adenosine Triphosphate Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

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