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Protein kinase C epsilon

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https://www.readbyqxmd.com/read/29535186/g-protein-%C3%AE-%C3%AE-subunits-directly-interact-with-and-activate-phospholipase-c%C3%AE%C2%B5
#1
Jerry C Madukwe, Elisabeth E Garland-Kuntz, Angeline M Lyon, Alan V Smrcka
Phospholipase C (PLC) enzymes hydrolyze membrane phosphatidylinositol 4,5 bisphosphate (PIP2) and regulate Ca2+ and protein kinase signaling in virtually all mammalian cell types. Chronic activation of the PLCɛ isoform downstream of G protein-coupled receptors (GPCRs) contributes to the development of cardiac hypertrophy. We have previously shown that PLCε-catalyzed hydrolysis of Golgi-associated phosphatidylinositol 4-phosphate (PI4P) in cardiac myocytes depends on G protein βγ subunits released upon stimulation with endothelin-1...
March 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29500928/epac-pkc%C3%AE%C2%B5-signalling-mediates-chronic-morphine-induced-expression-of-p2x3-receptors-in-rat-dorsal-root-ganglia
#2
Wenying Wang, Xiaqing Ma, Limin Luo, Min Huang, Jing Dong, Xiaoli Zhang, Wei Jiang, Tao Xu
BACKGROUND AND PURPOSE: The P2X3 receptor (P2X3R) is a major receptor in the processing of nociceptive information in dorsal root ganglia (DRGs). We investigated the role of the P2X3R and the detailed mechanisms underlying chronic morphine-induced analgesic tolerance in rats. EXPERIMENTAL APPROACHES: Under isoflurane inhalation anaesthesia, intrathecal catheters were implanted in male Sprague-Dawley rats. Repeated intrathecal (i.t.) morphine treatment was used to induce anti-nociceptive tolerance...
March 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29496994/fascin1-suppresses-rig-i-like-receptor-signaling-and-interferon-%C3%AE-production-by-associating-with-i%C3%AE%C2%BAb-kinase-%C3%AF%C2%B5-ikk-%C3%AF%C2%B5-in-colon-cancer
#3
Tomio Matsumura, Shigeaki Hida, Masato Kitazawa, Chifumi Fujii, Akira Kobayashi, Michiko Takeoka, Shun-Ichiro Taniguchi, Shin-Ichi Miyagawa
Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce IFN-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein retinoic acid-inducible gene I (RIG-I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets...
March 1, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29470978/contractile-responses-to-endothelin-1-are-regulated-by-pkc-phosphorylation-of-cardiac-myosin-binding-protein-c-in-rat-ventricular-myocytes
#4
Ioannis Smyrnias, Normann Goodwin, Dagmar Wachten, Jonas Skogestad, Jan Magnus Aronsen, Emma L Robinson, Kateryna Demydenko, Anne Segonds-Pichon, David Oxley, Sakthivel Sadayappan, Karin Sipido, Martin D Bootman, H Llewelyn Roderick
The shortening of sarcomeres that co-ordinates the pump function of the heart is stimulated by electrically-mediated increases in [Ca2+ ]. This process of excitation-contraction coupling (ECC) is subject to modulation by neurohormonal mediators that tune the output of the heart to meet the needs of the organism. Endothelin-1 (ET-1) is a potent modulator of cardiac function with effects on contraction amplitude, chronotropy and automaticity. The actions of ET-1 are evident during normal adaptive physiological responses and increased under pathophysiological conditions, such as following myocardial infarction and during heart failure, where ET-1 levels are elevated...
February 19, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29452158/protein-kinase-c-epsilon-mediates-the-inhibition-of-angiotensin-ii-on-the-slowly-activating-delayed-rectifier-potassium-current-through-channel-phosphorylation
#5
Xiangbo Gou, Wenying Wang, Sihao Zou, Yajuan Qi, Yanfang Xu
The slowly activating delayed rectifier K+ current (IKs ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates IKs through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of IKs by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record IKs in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes...
March 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29440987/metabolomics-based-identification-of-sirt5-and-protein-kinase-c-epsilon-regulated-pathways-in-brain
#6
Kevin B Koronowski, Nathalie Khoury, Kahlilia C Morris-Blanco, Holly M Stradecki-Cohan, Timothy J Garrett, Miguel A Perez-Pinzon
The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5-/-mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance. The aim of this study was to identify the SIRT5-regulated metabolic pathways in the brain and determine which of those pathways are linked to PKCε. Our results show SIRT5 is primarily expressed in neurons and endothelial cells in the brain, with mitochondrial and extra-mitochondrial localization...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29361366/physiologic-levels-of-resistin-induce-a-shift-from-proliferation-to-apoptosis-in-macrophage-and-vsmc-co-culture
#7
Mary C Zuniga, Gayatri Raghuraman, Wei Zhou
BACKGROUND: Resistin, an adipokine with inflammatory properties, has been associated with plaque vulnerability. Vascular smooth muscle cells and macrophages are the major cellular components in advanced atherosclerotic plaques and interdependently affect plaque stability. The purpose of this study was to examine the effects of resistin on the interactions of vascular smooth muscle cells and macrophages using co-culture systems. METHODS: Human monocytes were differentiated into macrophages...
April 2018: Surgery
https://www.readbyqxmd.com/read/29355553/new-application-of-the-commercial-sweetener-rebaudioside-a-as-a-hepatoprotective-candidate-induction-of-the-nrf2-signaling-pathway
#8
Yuxin Wang, Linyao Li, Yawen Wang, Xiaokang Zhu, Mingdong Jiang, Erqun Song, Yang Song
A large population of drug candidates have failed "from bench to bed" due to unwanted toxicities. We intend to develop an alternative approach for drug discovery, that is, to seek candidates from "safe" compounds. Rebaudioside A (Reb-A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found that Reb-A protects against carbon tetrachloride (CCl4 )-induced oxidative injury in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant activity on reducing cellular reactive oxygen species and malondialdehyde levels while increasing glutathione levels and superoxide dismutase and catalase activities...
March 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29198469/novel-small-molecule-inhibitors-of-protein-kinase-c-epsilon-reduce-ethanol-consumption-in-mice
#9
Angelo Blasio, Jingyi Wang, Dan Wang, Florence P Varodayan, Matthew B Pomrenze, Jacklyn Miller, Anna M Lee, Thomas McMahon, Sandeep Gyawali, Hua-Yu Wang, Marisa Roberto, Stanton McHardy, Michael A Pleiss, Robert O Messing
BACKGROUND: Despite the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, underscoring the need for new, effective medications. Previous results using protein kinase C epsilon (PKCε) knockout mice, RNA interference against PKCε, and peptide inhibitors of PKCε predict that small-molecule inhibitors of PKCε should reduce alcohol consumption in humans. METHODS: We designed a new class of PKCε inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor Y-27632...
December 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29175954/cd44-signaling-mediates-high-molecular-weight-hyaluronan-induced-antihyperalgesia
#10
Luiz F Ferrari, Eugen V Khomula, Dioneia Araldi, Jon D Levine
We studied, in male Sprague Dawley rats, the role of the cognate hyaluronan receptor, CD44 signaling in the antihyperalgesia induced by high molecular weight hyaluronan (HMWH). Low molecular weight hyaluronan (LMWH) acts at both peptidergic and nonpeptidergic nociceptors to induce mechanical hyperalgesia that is prevented by intrathecal oligodeoxynucleotide antisense to CD44 mRNA, which also prevents hyperalgesia induced by a CD44 receptor agonist, A6. Ongoing LMWH and A6 hyperalgesia are reversed by HMWH. HMWH also reverses the hyperalgesia induced by diverse pronociceptive mediators, prostaglandin E2 , epinephrine, TNFα, and interleukin-6, and the neuropathic pain induced by the cancer chemotherapy paclitaxel...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29021232/pkc%C3%AE%C2%B5-controls-mitotic-progression-by-regulating-centrosome-migration-and-mitotic-spindle-assembly
#11
Silvia Martini, Tanya Soliman, Giuliana Gobbi, Prisco Mirandola, Cecilia Carubbi, Elena Masselli, Giulia Pozzi, Peter J Parker, Marco Vitale
To form a proper mitotic spindle, centrosomes must be duplicated and driven poleward in a timely and controlled fashion. Improper timing of centrosome separation and errors in mitotic spindle assembly may lead to chromosome instability, a hallmark of cancer. Protein kinase C epsilon (PKCε) has recently emerged as a regulator of several cell-cycle processes associated with the resolution of mitotic catenation during the metaphase-anaphase transition and in regulating the abscission checkpoint. However, an engagement of PKCε in earlier (pre)mitotic events has not been addressed...
January 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28783756/pkc-epsilon-deficiency-alters-progenitor-cell-populations-in-favor-of-megakaryopoiesis
#12
John C Kostyak, Elisabetta Liverani, Satya P Kunapuli
BACKGROUND: It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCε remains elusive. OBJECTIVE: To delineate the role of PKCε in megakaryopoiesis. APPROACH AND RESULTS: We used a PKCε knockout mouse model to examine the effect of PKCε deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution...
2017: PloS One
https://www.readbyqxmd.com/read/28715866/protective-effects-of-isorhamnetin-on-n2a-cell-against-endoplasmic-reticulum-stress-induced-injury-is-mediated-by-pkc%C3%AE%C2%B5
#13
Lingyu Qiu, Yurong Ma, Yougen Luo, Zigang Cao, Huiqiang Lu
Endoplasmic reticulum stress (ERS)-induced intracellular calcium (Ca(2+)) overload and ROS burst plays a critical role in apoptosis. Protein kinase C epsilon (PKCε) is involved in regulating the homeostasis of Ca(2+) and ROS production. isorhamnetin (Iso), as an ROS scavenger, effectively inhibit apoptosis, but the mechanism is still unclear. This study was to investigate whether Iso can inhibit ERS-induced apoptosis in N2a cells, and the protective effects are involved in PKCε-mediated Ca(2+) homeostasis and inhibition of ROS...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621704/sensitization-of-trpv1-and-trpa1-via-peripheral-mglur5-signaling-contributes-to-thermal-and-mechanical-hypersensitivity
#14
Kuniya Honda, Masamichi Shinoda, Masahiro Kondo, Kohei Shimizu, Hisashi Yonemoto, Katsuhiko Otsuki, Ryuta Akasaka, Akihiko Furukawa, Koichi Iwata
Peripheral tissue inflammation or injury causes glutamate release from nociceptive axons, keratinocytes, and Schwann cells, resulting in thermal hypersensitivity. However, the detailed molecular mechanisms underlying glutamate-induced thermal hypersensitivity are unknown. The aim of this study was to clarify the involvement of peripheral transient receptor potential (TRP) TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and protein kinase C epsilon (PKCε) in glutamate-induced pain hypersensitivity. The amount of glutamate in the facial tissue was significantly increased 3 days after facial Complete Freund's adjuvant injection...
September 2017: Pain
https://www.readbyqxmd.com/read/28585865/protein-kinase-c-epsilon-delays-latency-until-anoxic-depolarization-through-arc-expression-and-glur2-internalization
#15
Charles H Cohan, Holly M Stradecki-Cohan, Kahlilia C Morris-Blanco, Nathalie Khoury, Kevin B Koronowski, Mehdi Youbi, Clinton B Wright, Miguel A Perez-Pinzon
Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that PKCɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc)...
December 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28497265/proteomics-analysis-of-pleomorphic-adenoma-of-the-human-parotid-gland
#16
Ahmet Mutlu, Murat Ozturk, Gurler Akpinar, Murat Kasap, Aylin Kanli
The objective of this study is to perform proteomic analysis of pleomorphic adenoma (PA) in the human parotid gland (PG) with comparison of normal PG. This is an individual prospective randomized controlled trial. This study was performed in a tertiary referral center. Tissue samples of PG and PA were taken after surgical excision of PG from 13 patients. Protein extracts were prepared and protein pools created from the soluble extracts were subjected to 2D-DIGE analysis. Proteins displaying regulation in their abundance were determined and identified using MALDIT-OF/TOF analysis...
August 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28494749/alcohol-addiction-metabotropic-glutamate-receptor-subtype-5-and-its-ligands-how-they-all-come-together
#17
Jaya Kumar, Zalina Ismail, Nurul Hazwani Hatta, Najwa Baharuddin, Hermizi Hapidin, Yvonne-Tee Get Bee, Ernie Yap, Rashidi Mohamed Pakri Mohamed
In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity...
May 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28482641/bryostatin-effects-on-cognitive-function-and-pkc%C3%A9-in-alzheimer-s-disease-phase-iia-and-expanded-access-trials
#18
Thomas J Nelson, Miao-Kun Sun, Chol Lim, Abhik Sen, Tapan Khan, Florin V Chirila, Daniel L Alkon
Bryostatin 1, a potent activator of protein kinase C epsilon (PKCɛ), has been shown to reverse synaptic loss and facilitate synaptic maturation in animal models of Alzheimer's disease (AD), Fragile X, stroke, and other neurological disorders. In a single-dose (25 μg/m2) randomized double-blind Phase IIa clinical trial, bryostatin levels reached a maximum at 1-2 h after the start of infusion. In close parallel with peak blood levels of bryostatin, an increase of PBMC PKCɛ was measured (p = 0.0185) within 1 h from the onset of infusion...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28402859/protein-kinase-c-epsilon-cooperates-with-pten-loss-for-prostate-tumorigenesis-through-the-cxcl13-cxcr5-pathway
#19
Rachana Garg, Jorge M Blando, Carlos J Perez, Martin C Abba, Fernando Benavides, Marcelo G Kazanietz
PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB) pathway...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28382133/the-controversial-role-of-phospholipase-c-epsilon-plc%C3%AE%C2%B5-in-cancer-development-and-progression
#20
REVIEW
Anna Tyutyunnykova, Gennady Telegeev, Anna Dubrovska
The phospholipase C (PLC) enzymes are important regulators of membrane phospholipid metabolism. PLC proteins can be activated by the receptor tyrosine kinases (RTK) or G-protein coupled receptors (GPCR) in response to the different extracellular stimuli including hormones and growth factors. Activated PLC enzymes hydrolyze phosphoinositides to increase the intracellular level of Ca(2+) and produce diacylglycerol, which are important mediators of the intracellular signaling transduction. PLC family includes 13 isozymes belonging to 6 subfamilies according to their domain structures and functions...
2017: Journal of Cancer
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