The structural basis of the autoinhibition mechanism of glycogen synthase kinase 3β (GSK3β): molecular modeling and molecular dynamics simulation studies

Mou, Linkai; Dou, Wenwen; Ma, Gang; Sun, Kening; Chen, Xiangyu

doi:10.1080/07391102.2019.1615988

Cited by 3 publications

(1 citation statement)

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“…Changes in the intracellular P2X7 receptor distribution result in the alteration of the immunoreactivity of the enzyme p-GSK3 β ( Figure 3(a) ). This enzyme is negatively regulated by phosphorylation in serine 9 and 21 residues located in its N-terminal, decreasing its catalytic activity [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Caused by Ozone Exposure Induces Changes in P2X7 Receptors, Neuroinflammation, and Neurodegeneration in the Rat Hippocampus

Velázquez-Pérez

Rodrı́guez-Martı́nez

Valdés-Fuentes

et al. 2021

Oxidative Medicine and Cellular Longevity

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Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5 ′ triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-β (GSK3-β) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 β) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-β at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%