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Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The phosphate group is hydrolyzed back to an OH– group by enzymes referred to as phosphatases, and the process is known as dephosphorylation. Protein phosphatase 1 (PP1) dephosphorylates a variety of proteins as well as K+ and Ca2+ channels, NMDA, and AMPA glutamate receptors. Protein phosphatase 2A (PP2A) also dephosphorylates a range of proteins that overlap with those of PP1, in addition to tau protein that stabilizes microtubules of the cytoskeleton. Excessive phosphorylation of tau protein is associated with Alzheimer’s disease. Protein phosphatase 2B (PP2B), also known as calcineurin, is abundant in neurons and is activated by Ca2+. It activates T cells of the immune system and dephosphorylates AMPA receptors. Protein phosphorylation and dephosphorylation are of fundamental importance in cell functioning as it is the major molecular mechanism through which protein activity in a cell is regulated both in and outside the nervous system.
Subneuronal Processing of Information by Solitary Waves and Stochastic Processes
Published in Sergey Edward Lyshevski, Nano and Molecular Electronics Handbook, 2018
Danko D. Georgiev, James F. Glazebrook
Microtubules do not only regulate motor protein function but also attach with their C–terminal tubulin tails different MAPs and protein kinases and phosphatases, thus organizing the intraneuronal space. The proper attachment/detachment of these proteins could regulate their enzymatic activity. In case studies of schizophrenia, there was found an altered expression of MAP2 and MAP5 that results in abnormalities in the neuronal cytoarchitecture [6]. In the case of Alzheimer’s disease, the primary alteration is the phosphorylation status of axonal MAP–tau and the activity of microtubule bound protein phosphatase 2A (PP2A) regulated via the attachment/detachment to microtubules [98].
Relaxation Oscillators
Published in James E. Ferrell, Systems Biology of Cell Signaling, 2021
Four particular regulatory proteins that are targets of active Cdk1 are of special importance for this regulatory circuit. The first is the Greatwall kinase (Gwl), which is activated by Cdk1 and then inactivates the phosphatase PP2A-B55 by phosphorylating and activating a pair of stoichiometric inhibitors of PP2A-B55 (ENSA and ARPP19). PP2A-B55 is the phosphatase responsible for dephosphorylating many of the substrates that Cdk1 phosphorylates, so the inactivation of PP2A-B55 potentiates the effect of Cdk1 activation.
Adverse health effects and stresses on offspring due to paternal exposure to harmful substances
Published in Critical Reviews in Environmental Science and Technology, 2023
Jiaqi Sun, Miaomiao Teng, Fengchang Wu, Xiaoli Zhao, Yunxia Li, Lihui Zhao, Wentian Zhao, Keng Po Lai, Kenneth Mei Yee Leung, John P. Giesy
Adult sire BALB/c mice exposed to MC-LR gave birth to offspring with reduced litter size and weight of pups and abnormalities of the lung (Meng et al., 2020). The mechanisms of the toxic effects are shown in Figure 4. After exposure to MC-LR, multiple piRNAs in sperm were downregulated, and pulmonary pathology resulted in abnormal activation of Wnt/β-catenin signaling to MC-LR. A large number of piRNA-rich target genes involved in the regulation of the embryo implantation pathway were downregulated. The expression of heat shock protein 90 α (hsp90α), protein phosphatase 2A (PP2A) and heat shock factor 1 (Hsf1) was inhibited in the testes of male mice after exposure to MC-LR, making the tissues and cells unprotected from stresses such as oxidative stress. Such changes were found to result in abnormal activation of the catenin signaling pathway, Wnt/β, in lung tissues of the offspring (Xu et al., 2008). In addition, it was found that acute administration of stress-sensitive glucocorticoid receptor agonists (using the ordinary glucocorticoid dexamethasone (Dex)) would affect the RNA payload of mature sperm within three hours after exposure (Gapp et al., 2021). It further affects the transcriptional trajectory of early embryos determined by single embryo sequencing and the metabolism of offspring.
Circular RNA expression profiles following MC-LR treatment in human normal liver cell line (HL7702) cells using high-throughput sequencing analysis
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Shuilin Zheng, Cong Wen, Shu Yang, Yue Yang, Fei Yang
More than 100 naturally occurring variants of MCs were identified with a common chemical structure cyclo-(D-Ala-X-D-MeAsp-Y-Adda-D-Glu-Mdha-), where X and Y represent variable L-amino acids (Wei et al. 2019, Yang et al. 2018a, 2019). Of these variants, microcystin-LR (MC-LR) is the most abundant and toxic, and persists in the environment for months (Chorus et al. 2000; Wu et al. 2019; Yang et al. 2018d). In order to reduce health risks associated with MC-LR exposure, the World Health Organization [World Health Organization (WHO), 1998] set a provisional upper value of 1 µg/L MC-LR in drinking water resources and this guideline level was adopted by many countries including China, USA, and Australia. Cao et al. (2019a, 2019b) also reported that MC-LR produced adverse effects on the gastrointestinal and cardiovascular systems. However, the primary target tissue for MC-LR- mediated damage is the liver (Chen et al. 2019b; Yang et al. 2018b; Zurawell et al. 2005). MacKintosh et al. (1990) proposed that inhibition of the activity of protein phosphatase 1 (PP1) and protein phosphatase2A (PP2A) might be the molecular mechanism underlying MC-LR-induced acute and chronic liver dysfunctions. Subsequent to enzymic phosphoproteins inhibition, gene expression, DNA repair systems, oxidative stress, and apoptosis were noted (Campos and Vasconcelos 2010; Chen et al. 2019a, 2019b). However, the complex interactive molecular mechanisms underlying MC-LR-mediated hepatic toxicity still remain to be determined.
Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Fei Yang, Cong Wen, Shuilin Zheng, Shu Yang, Jihua Chen, Xiangling Feng
Protein phosphatase 2A (PP2A) activity was measured according to manufacturer’s instructions (Promega, USA). After incubation with MC-LR, cells were collected, lysed to obtain the protein fraction, and endogenous phosphates eliminated as described by Yang et al. (2018). The cellular protein samples were added to the mixture solution containing 1 mM phosphopeptide substrate and incubated at 37°C for 30 min. Subsequently, 50 µl molybdate dye-additive mixture was added to stop the reaction. The absorbance was measured at 630 nm after 15 min, and PP2A activity expressed as pmol/µg protein/min.