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https://www.readbyqxmd.com/read/29050279/ssecks-akap12-scaffolding-functions-suppress-b16f10-induced-peritoneal-metastasis-by-attenuating-cxcl9-10-secretion-by-resident-fibroblasts
#1
Masashi Muramatsu, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Shin Akakura, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein known to suppress metastasis by attenuating tumor-intrinsic PKC- and Src-mediated signaling pathways [1]. In addition to downregulation in metastatic cells, in silico analyses identified SSeCKS downregulation in prostate or breast cancer-derived stroma, suggesting a microenvironmental cell role in controlling malignancy. Although orthotopic B16F10 and SM1WT1[Braf(V600E)] mouse melanoma tumors grew similarly in syngeneic WT or SSeCKS-null (KO) mice, KO hosts exhibited 5- to 10-fold higher levels of peritoneal metastasis, and this enhancement could be adoptively transferred by pre-injecting naïve WT mice with peritoneal fluid (PF), but not non-adherent peritoneal cells (PC), from naïve KO mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050205/catalpol-protects-synaptic-proteins-from-beta-amyloid-induced-neuron-injury-and-improves-cognitive-functions-in-aged-rats
#2
Zhiming Xia, Fengfei Wang, Shuang Zhou, Rui Zhang, Fushun Wang, Jason H Huang, Erxi Wu, Yongfang Zhang, Yaer Hu
Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in aged rat models...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049849/regulatory-connection-between-the-expression-level-of-classical-protein-kinase-c-and-pruning-of-climbing-fibers-from-cerebellar-purkinje-cells
#3
Nobutaka Takahashi, Anton N Shuvaev, Ayumu Konno, Yasunori Matsuzaki, Masashi Watanave, Hirokazu Hirai
Cerebellar Purkinje cells (PCs) express two members of the classical protein kinase C (PKC) subfamily, namely, PKCα and PKCγ. Previous studies on PKCγ knockout (KO) mice have revealed a critical role of PKCγ in the pruning of climbing fibers (CFs) from PCs during development. The question remains as to why only PKCγ and not PKCα is involved in CF synapse elimination from PCs. To address this question, we assessed the expression levels of PKCγ and PKCα in wild-type (WT) and PKCγ KO PCs using PC-specific quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analysis...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29048609/two-novel-atypical-pkc-inhibitors-acpd-and-dnda-effectively-mitigate-cell-proliferation-and-epithelial-to-mesenchymal-transition-of-metastatic-melanoma-while-inducing-apoptosis
#4
Wishrawana S Ratnayake, André H Apostolatos, David A Ostrov, Mildred Acevedo-Duncan
Atypical protein kinase Cs (aPKC) are involved in cell cycle progression, tumorigenesis, cell survival and migration in many cancers. We believe that aPKCs play an important role in cell motility of melanoma by regulating cell signaling pathways and inducing epithelial to mesenchymal transition (EMT). We have investigated the effects of two novel aPKC inhibitors; 2-acetyl-1,3-cyclopentanedione (ACPD) and 3,4-diaminonaphthalene-2,7-disulfonic acid (DNDA) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes...
September 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039083/myristoylated-alanine-rich-c-kinase-substrate-marcks-a-multirole-signaling-protein-in-cancers
#5
REVIEW
Lon Wolf R Fong, David C Yang, Ching-Hsien Chen
Emerging evidence implicates myristoylated alanine-rich C-kinase substrate (MARCKS), a major substrate of protein kinase C (PKC), in a critical role for cancer development and progression. MARCKS is tethered to the plasma membrane but can shuttle between the cytosol and plasma membrane via the myristoyl-electrostatic switch. Phosphorylation of MARCKS by PKC leads to its translocation from the plasma membrane to the cytosol where it functions in actin cytoskeletal remodeling, Ca(2+) signaling through binding to calmodulin, and regulation of exocytic vesicle release in secretory cells such as neurons and airway goblet cells...
October 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29032894/atypical-pkc-pkc%C3%AE-%C3%AE-activates-%C3%AE-secretase-and-increases-a%C3%AE-1-40-42-and-phospho-tau-in-mouse-brain-and-isolated-neuronal-cells-and-may-link-hyperinsulinemia-and-other-apkc-activators-to-development-of-pathological-and-memory-abnormalities-in-alzheimer-s-disease
#6
Mini P Sajan, Barbara C Hansen, Margaret G Higgs, C Ron Kahn, Ursula Braun, Michael Leitges, Collin R Park, David M Diamond, Robert V Farese
Hyperinsulinemia activates brain Akt and PKC-λ/ι and increases Aβ1-40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Aβ1-40/42, β-secretase activity was increased in insulin-resistant mice and monkeys. In insulin-resistant mice, inhibition of hepatic PKC-λ/ι sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously reversed increases in Akt, atypical protein kinase C (aPKC), β-secretase, and Aβ1-40/42, and restored acute Akt activation...
September 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29032483/regulation-of-cardiac-voltage-gated-sodium-channel-by-kinases-roles-of-protein-kinases-a-and-c
#7
Ademuyiwa S Aromolaran, Mohamed Chahine, Mohamed Boutjdir
In the heart, voltage-gated sodium (Nav) channel (Nav1.5) is defined by its pore-forming α-subunit and its auxiliary β-subunits, both of which are important for its critical contribution to the initiation and maintenance of the cardiac action potential (AP) that underlie normal heart rhythm. The physiological relevance of Nav1.5 is further marked by the fact that inherited or congenital mutations in Nav1.5 channel gene SCN5A lead to altered functional expression (including expression, trafficking, and current density), and are generally manifested in the form of distinct cardiac arrhythmic events, epilepsy, neuropathic pain, migraine, and neuromuscular disorders...
October 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29032001/efficacy-of-self-retained-cryopreserved-amniotic-membrane-for-treatment-of-neuropathic-corneal-pain
#8
Melina I Morkin, Pedram Hamrah
PURPOSE: Treatment of neuropathic corneal pain (NCP) remains intricate, and involves a long-term combined multistep approach. The self-retained cryopreserved amniotic membrane (PROKERA(®), Bio-Tissue, Miami,FL) has been utilized for multiple ocular surface disorders. We evaluate the efficacy, safety, and tolerability of ProKera(®) Slim [PKS] and ProKera(®) Clear [PKC] in the treatment of NCP. METHODS: Retrospective case series of 9 patients who received PKS/PKC for the acute treatment of NCP...
October 12, 2017: Ocular Surface
https://www.readbyqxmd.com/read/29030553/actomyosin-polarisation-through-plc-pkc-triggers-symmetry-breaking-of-the-mouse-embryo
#9
Meng Zhu, Chuen Yan Leung, Marta N Shahbazi, Magdalena Zernicka-Goetz
Establishment of cell polarity in the mammalian embryo is fundamental for the first cell fate decision that sets aside progenitor cells for both the new organism and the placenta. Yet the sequence of events and molecular mechanism that trigger this process remain unknown. Here, we show that de novo polarisation of the mouse embryo occurs in two distinct phases at the 8-cell stage. In the first phase, an apical actomyosin network is formed. This is a pre-requisite for the second phase, in which the Par complex localises to the apical domain, excluding actomyosin and forming a mature apical cap...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29030286/peptides-acting-as-cognitive-enhancers
#10
Diego Asua, Ghassen Bougamra, María Calleja, Miguel Morales, Shira Knafo
The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signalling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory...
October 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29029445/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#11
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029387/the-%C3%AE-nad-salvage-pathway-and-pkc-mediated-signaling-influence-localized-parp-1-activity-and-ctcf-poly-adp-ribosylation
#12
David J P Henderson, Jj L Miranda, Beverly M Emerson
Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029020/the-endometrial-polarity-paradox-differential-regulation-of-polarity-within-secretory-phase-human-endometrium
#13
Sarah Whitby, Lois A Salamonsen, Jemma Evans
A major cause of infertility in normal and assisted reproduction cycles is failure of the endometrium to undergo appropriate changes during the secretory phase of the menstrual cycle as it acquires receptivity for an implanting blastocyst. Current dogma states that loss of epithelial polarity in the luminal epithelial cells, the point of first contact between maternal endometrium and blastocyst, may facilitate embryo implantation. Loss of polarity is likely an important change during the secretory phase to overcome mutual repulsion between otherwise polarised epithelial surfaces...
September 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/29027985/triterpenoids-from-ocimum-labiatum-activates-latent-hiv-1-expression-in-vitro-potential-for-use-in-adjuvant-therapy
#14
Petrina Kapewangolo, Justin J Omolo, Pascaline Fonteh, Martha Kandawa-Schulz, Debra Meyer
Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART)...
October 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29024239/phosphorylation-responsive-membrane-transport-of-peptides
#15
Shu Peng, Andrea Barba-Bon, Yu-Chen Pan, Werner M Nau, Dong-Sheng Guo, Andreas Hennig
Phosphorylation and dephosphorylation of peptides by kinases and phosphatases is essential for signal transduction in biological systems and many diseases involve abnormal activities of these enzymes. Herein, we introduce amphiphilic calixarenes as key components for supramolecular, phosphorylation-responsive membrane transport systems. Dye efflux experiments with liposomes demonstrated that calixarenes are highly active counterion activators for established cell-penetrating peptides with EC50 values in the low nanomolar range...
October 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29022192/a-positive-circuit-of-vegf-increases-glut-1-expression-by-increasing-hif-1%C3%AE-gene-expression-in-human-retinal-endothelial-cells
#16
Yoon Kyung Choi
Treatment of human retinal microvascular endothelial cells (HRMECs) with vascular endothelial growth factor 165 (VEGF165) increased hypoxia-inducible factor 1α (HIF-1α), VEGF, and glucose transporter 1 (Glut-1) mRNA expression and Glut-1 protein localization to the membrane. In contrast, treatment of human retinal pigment epithelium cells with VEGF165 did not induce HIF-1α, VEGF, and Glut-1 gene expression. Microvascular endothelial cells are surrounded by astrocytic end feet in the retina. Astrocyte-derived A-kinase anchor protein 12 overexpression during hypoxia downregulated VEGF secretion, and this conditioned medium reduced VEGF and Glut-1 expression in HRMECs, suggesting that communications between astrocytes and endothelial cells may be the determinants of the blood vessel network...
October 11, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#17
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29021339/phosphorylation-regulates-connexin43-zo-1-binding-and-release-an-important-step-in-gap-junction-turnover
#18
Anastasia F Thévenin, Rachel A Margraf, Charles G Fisher, Rachael M Kells-Andrews, Matthias M Falk
To investigate whether connexin phosphorylation regulates ZO-1's known role in gap junction (GJ) function, we generated and analyzed a series of phosphomimetic and phosphorylation-dead mutants by exchanging known conserved regulatory serine (S) residues 255, 279/282, 365, 368, and 373 located in the C-terminal domain of connexin43 (Cx43) into glutamic acid (E) or alanine (A) residues. All connexin mutants were translated into stable, full-length proteins and assembled into GJs when expressed in HeLa or MDCK cells...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29020306/lithium-and-tamoxifen-modulate-behavior-and-protein-kinase-c-activity-in-the-animal-model-of-mania-induced-by-ouabain-behavior-and-pkc-activity-in-animal-model
#19
Samira S Valvassori, Gustavo C Dal-Pont, Wilson R Resende, Roger B Varela, Bruna R Peterle, Fernanda F Gava, Franciele G Mina, José H Cararo, André F Carvalho, João Quevedo
Background: The intracerebroventricular (ICV) injection of ouabain, a specific inhibitor of the Na+/K+-adenosine-triphosphatase (Na+/K+-ATPase) enzyme, induces hyperactivity in rats in a putative animal model of mania. Several evidences have suggested that protein kinase C (PKC) signaling pathway is involved in bipolar disorder (BD). In addition, it is known that protein kinase C (PKC) inhibitors, such as lithium (Li) and tamoxifen (TMX), are effective in treating acute mania. Methods: In the present study, we investigated the effects of Li and TMX on PKC signaling pathway in the frontal cortex and hippocampus of rats submitted to the animal model of mania induced by ouabain...
August 7, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29016360/pkc%C3%AE-dependent-upregulation-of-p27kip1-contributes-to-oxidative-stress-induced-retinal-pigment-epithelial-cell-multinucleation
#20
Dinusha Rajapakse, Mei Chen, Tim M Curtis, Heping Xu
Retinal pigment epithelial (RPE) cells increase in size and multinucleate during aging. We have shown using human and mouse cell lines that oxidised photoreceptor outer segments (oxPOS)-induced cytokinesis failure is related to RPE cell multinucleation, although the underlying mechanism remains unknown. This study investigated the role of the PKC pathway in oxPOS-induced RPE multinucleation using ARPE19 cells. oxPOS treatment promoted PKC activity and upregulated the mRNA expression of PKC α, δ, ζ, ι and μ...
October 9, 2017: Aging
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