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Role of Vitamin D and Antioxidants in the Prevention and Treatment of Alzheimer’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Shilia Jacob Kurian, Ruby Benson, Sonal Sekhar Miraj, Mahadev Rao
Dysregulation in intracellular calcium signaling is widely implicated in the pathophysiology of AD, which results in lesions, hyperphosphorylation of tau, and finally neurodegeneration. Mitochondrial activities largely depend on calcium from the endoplasmic reticulum (ER) or extracellular space. Inositol 1,4,5-trisphosphate (IP3) is the second messenger and the inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular ion channels, which stimulate the release of calcium from the ER (Bizzarri et al. 2016; Egorova and Bezprozvanny 2018).
Cognition Enhancers
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Ramneek Kaur, Rashi Rajput, Sachin Kumar, Harleen Kaur, R. Rachana, Manisha Singh
In protein kinase B (PKB) signaling pathway, TrkB acts over sequences of phosphorylation steps involving Akt, mammalian target of rapamycin (which controls translation of mRNA), and PI3K. It involves phospholipase Cγ whose function is to cleave the phospholipids at phosphate site, thus, forming 1, 2-diacylglycerol and inositol 1, 4, 5-triphosphate (IP3). IP3 is an essential secondary messenger for the IP3 receptor on endoplasmic reticulum (ER) that is a main constituent of ryanodine receptor (RyR) and calcium-induced calcium release (Song et al., 2005).
B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Many of the biochemical steps in B cell activation are still being elucidated. With respect to signalling via the Ig receptor, the PTK syk may initially phosphorylate Ig-α and -β, permitting their interaction with a host of other PTKs such as blk, fyn, lck, and lyn (Figure 5–13). Phospholipase C γ (PLCγ) then associates with the receptor complex, its activity is further regulated by a G (GTP-dependent) protein. PLC cleaves phosphatidylinositolbisphosphate (PIP2) yielding inositoltriphosphate (IP3) and diacylglycerol (DAG). DAG is essential for the action of protein kinase C (PKC). IP3 causes release of intracellular calcium stores and influx of extracellular calcium. PKC and calcium-dependent kinases in turn phosphorylate other membrane proteins, other kinases, and transcription factors, leading to all of the phenotypic and genetic changes associated with cellular activation.
Hyperoside ameliorates cerebral ischaemic–reperfusion injury by opening the TRPV4 channel in vivo through the IP3-PKC signalling pathway
Published in Pharmaceutical Biology, 2023
Lei Shi, Chenchen Jiang, Hanghang Xu, Jiangping Wu, Jiajun Lu, Yuxiang He, Xiuyun Yin, Zhuo Chen, Di Cao, Xuebin Shen, Xuefeng Hou, Jun Han
Accumulating evidence has shown that TRPV4 activation influences vascular dilation by inducing the production of EDHF, NO or PGI2 (Liu et al. 2021). Similar to previous studies, we also found that Hyp-induced vasodilatation is dependent on EDHF production in an NO- and PGI2-independent manner in endothelial cells from the CBA of IR rats. To further investigate the mechanism by which Hyp affects TRPV4 expression, we focused on IP3 and PKC. IP3-associated and PKC-mediated signalling pathways play a critical role in inducing PGI2- and NO-independent vasodilation. IP3 is an important second messenger that binds to inositol triphosphate receptors on the sarcoplasmic reticulum to cause Ca2+ release and an increase in intracellular Ca2+ concentration (Ivanova et al. 2017). Studies have shown that IP3 activation promotes the opening of TRPV4 channels (Heathcote et al. 2019). PKC induces vasodilation through the EDHF mechanism by activating TRPV4, which plays an important role in regulating vasomotor function (Sonkusare et al. 2014). The results herein showed that the expression of IP3R and PKC was markedly increased by the Hyp treatment, and this effect was reduced by treatment with an IP3R inhibitor (2APB) or an inhibitor of PKC (BisI). Importantly, the effect of Hyp on TRPV4 expression was considerably suppressed by the 2APB and BisI treatment, suggesting that Hyp upregulates TRPV4 expression through the activation of the IP3 and PKC signalling pathways.
An appraisal of vascular endothelial growth factor (VEGF): the dynamic molecule of wound healing and its current clinical applications
Published in Growth Factors, 2022
Aakansha Giri Goswami, Somprakas Basu, Farhanul Huda, Jayanti Pant, Amrita Ghosh Kar, Tuhina Banerjee, Vijay Kumar Shukla
VEGFR-1, 2, and 3 are transmembrane proteins with tyrosine kinase activity (Olofsson et al. 1998). The exact mechanism of VEGF-induced intracellular activity is still a subject of intense study. Broadly, it appears that VEGF binding with the extracellular domains causes autophosphorylation of the receptor. This leads to activation of phospholipase Cγ, which activates protein kinase C and catalyzes the conversion of phosphatidylinositol 4,5-biphosphate (PIP2) to inositol 1,4,5-triphosphate (IP3) and diacylglycerol (Shibuya 2001). Finally, MAP-kinase (mitogen-activated protein kinase) activation leads to gene expression (Waltenberger et al. 1994). Although VEGFR-1 has the highest affinity for VEGF, its activation has very weak transcription effects, which puts a question mark on its true role in stimulating angiogenesis. On the other hand, VEGFR-2 is expressed significantly more than its counterpart and demonstrates 10 times more tyrosine kinase activity, which makes VEGFR-2 as the main mediator of VEGF function and a probable target for pharmacological intervention (Waltenberger et al. 1994). On the other hand, binding to its soluble receptors does not induce gene transcription and limits VEGF activity. It appears that VEGFR-1 and sVEGFR-1, 2 control VEGF overexpression and help in maintaining an angiogenic homeostasis.
The Wnt/β-catenin pathway in breast cancer therapy: a pre-clinical perspective of its targeting for clinical translation
Published in Expert Review of Anticancer Therapy, 2022
Dezaree Raut, Amisha Vora, Lokesh Kumar Bhatt
The non-canonical Wnt signaling pathway, also known as the β-catenin-independent pathway, is divided into the Wnt/Ca2+ pathway and planar cell polarity (PCP) pathway. In the Wnt/Ca2+ pathway, when Wnt binds to the frizzled (Fz) receptor, it causes intracellular binding of Dvl near the Fz receptor (FZD). In addition to Dvl, the Fz receptor also stimulated trimeric G-protein. Simultaneous stimulation of Dvl and D-protein can activate either Phospholipase (PLC) or Cyclic nucleotide phosphodiesterase (PDE). When PLC is activated, it causes activation of Inositol trisphosphate (IP3). IP3 causes an intracellular release of calcium which further causes calcineurin and CaMK11 activation. CaMK11 activates a nuclear factor of activated T-cells, responsible for cell adhesion, migrations, and tissue separation. On the other hand, calcineurin activates certain substances that interfere with the canonical Wnt signaling pathway to regulate dorsal axis formation negatively. If PDE gets activated, it causes inhibition of calcium release from ER. This pathway helps to regulate intracellular calcium levels by controlling the calcium release from the endoplasmic reticulum [16].