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Ischemic Inhibition of Calcium Slow Current in the Heart
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
High concentrations of the a-adrenergic agonist, phenylephrine, has been shown to cause a positive inotropic effect and to increase APD and to increase ICa in bovine cardiac muscle.11 There is still controversy with respect to the effect of activation of the a-adrenoceptors of myocardial cells on the level of cAMP, some investigators reporting increases and others finding no changes. However, the a-adrenoceptor stimulates the phosphatidyl inositol (PI) cycle and breakdown and generation of inositol trisphosphate (IP3) and diacyl glycerol (DG).10 IP3 has been implicated as a second messenger to act on the sarcoplasmic reticulum (SR) to release Ca2+ stored in this compartment. DG and Ca2+ activate protein kinase C, which phosphorylates a number of proteins. It is not known at present whether protein kinase C is involved in regulation of the myocardial Ca2+ slow channels.
Apoptosis: Cellular Signaling and Molecular Mechanisms
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Rosemary B. Evans, John A. Cidlowski
Alteration of intracellular Ca2+ concentration is not the only signal which can induce apoptosis. Indeed, Ca2+ is actually able to protect sympathetic nerve ganglion cells and pre-B cells (BAF-3) from apoptosis following removal of nerve growth factor and IL-3, respectively.38,39 In addition, apoptosis in thymocytes is inhibited if protein kinase C is activated by phorbol esters concurrently with an increase in intracellular Ca2+ concentration.2 Treatment of immature thymocytes with the T cell mitogen concanavalin A (Con A) causes activation of protein kinase C and an increase in intracellular Ca2+, ultimately leading to proliferation rather than programmed cell death.37 Apoptosis proceeds, however, if these cells are exposed to Con A in the presence of protein kinase C inhibitors. Clearly, activation of protein kinase C is able to inhibit apoptosis which would normally occur after an increase in intracellular Ca2+ levels. Indeed, protein kinase C activity blocks DNA degradation induced by Ca2+ in isolated thymocyte nuclei. Thus, some of the substrates upon which this kinase acts and which regulate apoptosis must be located in the nucleus.37 These data demonstrate that protein kinase C must act as a cellular signal that leads to proliferation in some instances and apoptosis in others. Additional studies are required to identify the substrates upon which protein kinase C acts in the apoptotic pathway in different cells.
Phosphoinositide Metabolism
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Phosphorylation of protein kinase C may contribute to regulate its activity. The enzyme can undergo autophosphorylation at multiple sites,215 and the resulting autophosphorylated kinase has a lower Ka for Ca2+ and a higher affinity for phorbol ester than the nonphosphorylated enzyme, but still requires Ca2+ and phospholipid for maximal activity. Compounds that interact with the catalytic site of protein kinase C, competing with ATP, act as inhibitors of the enzyme in a concentration-dependent manner.216 Casein kinase I, but not casein kinase II, can phosphorylate protein kinase C in the absence of Ca2+ and phospholipids.217 The possible role of autophosphorylation or trans-phosphorylation in the regulation of protein kinase activity in intact cells is not understood.
Ethanol extract of the mushroom Coprinus comatus exhibits antidiabetic and antioxidant activities in streptozotocin-induced diabetic rats
Published in Pharmaceutical Biology, 2022
Nuniek Ina Ratnaningtyas, Hernayanti Hernayanti, Nuraeni Ekowati, Fajar Husen
Diabetes mellitus (DM) is a metabolic disease associated with disordered carbohydrate metabolism and decreased or absence of insulin sensitivity and production. Diabetes mellitus is strongly associated with several diseases, including cardiovascular complications, heart attacks, and obesity, resulting in microvascular complications such as blood vessel sclerosis, which can progress to myocardial infarction (Sabo et al. 2010). The metabolic abnormalities associated with diabetes may result in an oxidative stress reaction in the pancreatic cell, adversely affecting insulin activity via multiple interacting pathways. Numerous signalling pathways in cells, for example, NF-κB (nuclear factor-κB) and PKC (protein kinase C), may interfere with insulin signalling pathways, resulting in the development of insulin resistance in type 2 diabetes patients; additionally, it may activate ROS (reactive oxygen species) and generate ROS such as hydrogen peroxide and superoxide anions. These species may deteriorate the pancreas’s Islets-cells, resulting in the decreased insulin release seen in diabetes mellitus (Ma et al. 2018).
Impact of SGLT2 inhibitors on the kidney in people with type 2 diabetes and severely increased albuminuria
Published in Expert Review of Clinical Pharmacology, 2022
Nasir Shah, Vlado Perkovic, Sradha Kotwal
Protein kinase C is a critical intracellular signaling molecule regulating vascular permeability, extracellular matrix synthesis, smooth muscle contraction, angiogenesis, cell growth, and differentiation [34]. Intracellular hyperglycemia increases de novo diacylglycerol synthesis activating protein kinase C which stimulates NADPH oxidase and the sodium/hydrogen exchanger producing superoxide and subsequent ROS formation [35,36]. In a diabetic rat model, the sodium/hydrogen exchanger has also been shown to increase expression of vascular endothelial growth factor, transforming growth factor-β (TGF-β), and extra-cellular matrix components [37–39]. TGF-β, a known fibrogenic cytokine, regulates cell proliferation, cellular differentiation and enhances the accumulation of extracellular matrix proteins in the kidney resulting in progressive renal disease [40,41].
Protein kinase C-θ knockout decreases serum IL-10 levels and inhibits insulin secretion from islet β cells
Published in Islets, 2021
Feng Hong, Yang Yang, Baiyi Chen, Peng Li, Guoguang Wang, Yuxin Jiang
As a member of the serine/threonine protein kinase family, protein kinase C (PKC) is represented by more than 10 different functional isozymes.1 Based on the structural differences, PKC can be classified into several categories: 1) classical, including α, β, and γ members; 2) novel, including δ, ε, and η; 3) atypical, including ζ and ι; and 4) PKC-related kinases (PRKs).2 PKCs participate in many biological processes including cell proliferation, differentiation, and apoptosis.3 Several PKC isoforms, such as PKC-α and PKC-ε, are present in the β cells of the pancreatic islets.4 Glucose stimulates PKC-α synthesis and promotes its translocation from the cytosol to the membrane.5,6 Inhibitors of both PKC-α and PKC-ε can decrease glucose-induced insulin secretion.7,8 PKC-δ is also expressed in pancreatic islet β cells and is essential for pancreatic β cell replication during insulin resistance.9