Phosphoinositide Metabolism
Enrique Pimentel in Handbook of Growth Factors, 2017
Inositol mono- and polyphosphate derivatives are produced during the hydrolysis of phosphatidylinositol. One of these products is 1,4,5-trisphosphate, which is generated through the metabolite intermediates, phosphatidylinositols 4-monophosphate and 4,5-bisphosphate. Inositol 1,4,5-trisphosphate may mobilize calcium ions from intracellular reservoirs and may regulate enzymic reactions or the permeability of the plasma membrane to monovalent cations. Although phosphoinositide turnover and rise in the [Ca2+]i is partly dependent on extracellular Ca2+, at least in some cellular systems there is an early Ca2+-independent rise in inositol 1,4,5-trisphosphate which precedes the rise in [Ca2+]i.66
Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart
H. Saito, Y. Yamori, M. Minami, S.H. Parvez in New Advances in SHR Research –, 2020
In many tissues, the physiologic second messenger mediating the intracellular response to α1-adrenergic stimulation is 1,4, 5-IP3. The metabolism of 1,4, 5-IP3. has been studied extensively in many types of tissues. The results of these studies indicate that dephosphorylation to 1, 4-IP2 and phosphorylation to 1, 3,4, 5-IP4 are the immediatemetabolic routes (Bradford and Irvine, 1987; Morris et al., 1988). The 1,4- IP2 is further dephosphorylated to inositol 4-monophosphate while 1, 3,4, 5-IP4 is dephosphorylated to form another isomer of inositol trisphosphate, 1,3,4-IP3. The 1, 4, 5-IP3 mobilizes intracellular Ca2+ and as such produces physiological alterations characteristic of specific hormonal stimulation. In human cardiac tissue, the α1-adrenergic receptor-mediated increase in IP3 has been previously reported. It was also reported that α1-adrenergic stimulation caused IP3 to accumulate in adult canine myocytes. These reports suggest that the accumulations of IP3 and IP4 after hormonal stimulation play a physiological role, possibly by altering Ca2+ levels in cardiac tissues. However, studies concerning the accumulation of inositol polyphosphate under pathophysiological conditions are few. We recently reported that IP3 release increased in cardiomyopathic hamster heart cells and IP3 kinase markedly increased in SHRSP heart . The present experiment investigated PIP2 breakdown and IP3 release was shown to increase in SHRSP hearts.
Eukaryotic Dna-Dependent Rna Polymerases: An Evaluation of Their Role in the Regulation of Gene Expression
Gerald M. Kolodny in Eukaryotic Gene Regulation, 2018
Hildebrandt and Sauer146 observed an inverse correlation between polyphosphate levels and RNA polymerase I activity during the growth cycle of Physarum. Polyphosphate (2 μΜ) caused 50% inhibition of enzyme I in vitro but less than 10% inhibition of form II and associated more tightly with the former enzyme than the latter (measured by 32P binding). Whether polyphosphates bind to the enzyme in vivo was not investigated.
Immunothrombosis and thromboinflammation in host defense and disease
Published in Platelets, 2021
Kimberly Martinod, Carsten Deppermann
Another key component of platelet granules which has been linked to procoagulant activity is inorganic polyphosphate [39], a negatively charged linear polymer of inorganic phosphate residues ranging in size from 60 to 100 phosphate residues on average [40]. Polyphosphate leads to factor XII activation and plasma kallikrein-mediated bradykinin production from kininogen [41], thus propagating thromboinflammation. Factor XII is also expressed by neutrophils, being translocated to the cell surface upon its activation [42], thus providing a potential mechanism for polyphosphate-mediated neutrophil activation. Indeed, platelet polyphosphate contributes to neutrophil activation toward NETosis via mTOR inhibition as shown invitro and in a mouse model of ferric chloride-induced thrombosis; this process is regulated by the cytokine IL-29 [43]. In an animal model of sepsis, platelet polyphosphate contributed to NET-induced thrombin generation but not to NET formation [44]. Platelet polyphosphate is thus broadly relevant in a wide variety of diseases where thrombosis is a key component, either directly by promoting coagulation or indirectly via neutrophil activation toward NET formation. Polyphosphate neutralization is indeed protective against thrombosis in in vivo animal models [45]. Furthermore, platelet high mobility group protein B1 (HMGB1) also plays a crucial role in NET formation in the context of both venous and arterial thrombosis [33,46,47]. This platelet-derived danger-associated molecular pattern can be either soluble [48] or carried on platelet microparticles [49].
pH-sensitive chitosan-deoxycholic acid/alginate nanoparticles for oral insulin delivery
Published in Pharmaceutical Development and Technology, 2021
Ya-Wen Zhang, Ling-Lan Tu, Zhan Tang, Qiao Wang, Gao-Li Zheng, Li-Na Yin
Insulin (28.1 U/mg) was bought from Xuzhou Wanbang Jinqiao Pharmaceutical Co., Ltd. (Xuzhou, China). Chitosan (89.1% degree of deacetylation, 126 KDa molecular weight) was bought from Golden-shell Biochemical Co. Ltd. (Zhejiang, China). Deoxycholic acid (DCA) was purchased from Aladdin (Shanghai, China). Fluorescein isothiocyanate (FITC) and 1-ethyl-3- (dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Sodium alginate was purchased from Shanghai Chemical Reagent Factory (Shanghai, China). Sodium polyphosphate was purchased from Tianjin Fuchen Chemical Reagent Factory (Tianjin, China). All the other chemicals and reagents were of analytical or HPLC grade.
Proteomic interrogation of antibiotic resistance and persistence in Escherichia coli – progress and potential for medical research
Published in Expert Review of Proteomics, 2020
Danfeng Zhang, Yuanqing Hu, Qiuqiang Zhu, Jiafu Huang, Yiyun Chen
Microbial polyphosphate kinase 1 (PPK1) catalyzes the synthesis of polyphosphates (Poly P) and is conserved across many bacterial species including pathogens. PPK1 activity is closely related to QS, biofilm formation, persistence and oxidative stress responses, establishing PPK as a possible target for anti-persister therapies [140]. Mesalamine, an inhibitor of PPK that rapidly decreases Poly Plevels invivo, could decrease the formation of ampicillin-tolerant persisters and biofilms by two to three orders of magnitude, and increase levels of inflammatory oxidants such as hypochlorous acid in uropathogenic E.coli, suggesting a potential application of mesalamine for preventing persistence [140].
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