Read by QxMD icon Read


Yuqing Wang, Shanshan Lu, Zhongwei Qu, Lin Wu, Yizheng Wang
GLT-1 is mainly expressed in astrocytes and has a crucial role in glutamate uptake. Sonic hedgehog (SHH) can inhibit glutamate uptake and its pathway is activated in many brain diseases related with glutamate excitotoxicity. However, whether SHH regulates GLT-1 to affect glutamate uptake is not clear. Here, we use pharmacological and genetic methods to show that SHH induces GLT-1 degradation in astrocytes in a manner that is dependent on PKC delta (PKCδ) to regulate GLT-1 activities. GLT-1 protein levels are reduced as early as 2 hs in astrocytes after incubation with SHH, whereas its mRNA levels are not changed...
December 4, 2017: Neuroscience
Cristina Solà-Adell, Patricia Bogdanov, Cristina Hernández, Joel Sampedro, Marta Valeri, Marta Garcia-Ramirez, Christian Pasquali, Rafael Simó
PURPOSE: The mechanisms involved in the reported beneficial effects of Calcium dobesilate monohydrate (CaD) for the treatment of diabetic retinopathy (DR) remain to be elucidated. The main aim of the present study is to examine whether CaD prevents early events in the pathogenesis of DR such as neurodegeneration and vascular leakage. In addition, putative mediators of both neurodegeneration (glutamate/GLAST, ET-1/ETB receptor) and early microvascular impairment (ET-1/ETA receptor, oxidative stress, VEGF, and the PKC-delta-p38 MAPK pathway) have been examined...
June 2, 2017: Current Eye Research
Manutea Serrero, Rémi Planès, Elmostafa Bahraoui
HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation...
May 24, 2017: Scientific Reports
Stefania Merighi, Serena Bencivenni, Fabrizio Vincenzi, Katia Varani, Pier Andrea Borea, Stefania Gessi
The hallmark of neuroinflammation is the activation of microglia, the immunocompetent cells of the CNS, releasing a number of proinflammatory mediators implicated in the pathogenesis of neuronal diseases. Adenosine is an ubiquitous autacoid regulating several microglia functions through four receptor subtypes named A1, A2A, A2B and A3 (ARs), that represent good targets to suppress inflammation occurring in CNS. Here we investigated the potential role of ARs in the modulation of IL-6 secretion and cell proliferation in primary microglial cells...
December 11, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Y Zaid, N Senhaji, Y Darif, K Kojok, M Oudghiri, A Naya
Platelet activation is a complex balance of positive and negative signaling pathways. Several protein kinase C (PKC) isoforms are expressed in human platelets. They are a major regulator of platelet granule secretion, activation and aggregation activity. One of those isoforms is the PKCδ isozyme, it has a central yet complex role in platelets such as opposite signaling functions depending on the nature of the agonist, it concentration and pathway. In fact, it has been shown that PKCδ has an overall negative influence on platelet function in response to collagen, while, following PAR stimulation, PKCδ has a positive effect on platelet function...
July 2016: Current Research in Translational Medicine
Shanthi Ganesan, Aileen F Keating
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI)...
February 1, 2016: Toxicology and Applied Pharmacology
J Radosinska, L H Kurahara, K Hiraishi, C Viczenczova, T Egan Benova, B Szeiffova Bacova, V Dosenko, J Navarova, B Obsitnik, I Imanaga, T Soukup, N Tribulova
Previous data suggest that type 1 diabetes mellitus leads to the deterioration of myocardial intercellular communication mediated by connexin-43 (Cx43) channels. We therefore aimed to explore Cx43, PKC signaling and ultrastructure in non-treated and omega-3 fatty acid (omega-3) treated spontaneously diabetic Goto-Kakizaki (GK) rats considered as type 2 diabetes model. Four-week-old GK and non-diabetic Wistar-Clea rats were fed omega-3 (200 mg/kg/day) for 2 months and compared with untreated rats. Real-time PCR and immunoblotting were performed to determine Cx43, PKC-epsilon and PKC-delta expression...
2015: Physiological Research
S Jarius, B Wildemann
Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa head antibodies' due their characteristic somatodendritic binding pattern when tested by immunohistochemistry)...
September 17, 2015: Journal of Neuroinflammation
Felicia Gerst, Gabriele Kaiser, Madhura Panse, Tina Sartorius, Anna Pujol, Anita M Hennige, Fausto Machicao, Reiner Lammers, Fatima Bosch, Hans-Ulrich Häring, Susanne Ullrich
AIMS/HYPOTHESIS: Forkhead box protein O1 (FOXO1) is a transcription factor essential for beta cell fate. Protein kinase B-dependent phosphorylation of FOXO1 at S256 (P-FOXO1) enables its binding to 14-3-3 dimers and nuclear export. Dephosphorylated FOXO1 enters nuclei and activates pro-apoptotic genes. Since our previous observations suggest that protein kinase C delta (PKCδ) induces nuclear accumulation of FOXO1, the underlying mechanism was examined. METHODS: In human islets, genetically modified mice and INS-1E cells apoptosis was assessed by TUNEL staining...
December 2015: Diabetologia
Yu Chen, Wen Wang, Fen Liu, Luosheng Tang, Renhong Tang, Wenjie Li
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus. But few efficient therapeutic methods have been reported. This study discussed the functions of 9-cis-retinoic acid (9-cis-RA) in sensitizing retinal pericytes to platelet-derived growth factor (PDGF)-BB. Using streptozotocin (STZ)-induced diabetic mice and high glucose-treated bovine retinal pericytes (BRPC), we analyzed the impacts of 9-cis-RA by detecting cell apoptosis via DNA fragmentation assay and detecting related factors through adenovirus or lentivirus infection and western blot...
October 2, 2015: Biochemical and Biophysical Research Communications
Patcharapong Thangsunan, Suriya Tateing, Supa Hannongbua, Nuttee Suree
Protein kinase C (PKC) isozymes are important regulatory enzymes that have been implicated in many diseases, including cancer, Alzheimer's disease, and in the eradication of HIV/AIDS. Given their potential clinical ramifications, PKC modulators, e.g. phorbol esters and bryostatin, are also of great interest in the drug development. However, structural details on the binding between PKC and its modulators, especially bryostatin - the highly potent and non-tumor promoting activator for PKCs, are still lacking...
July 2016: Journal of Biomolecular Structure & Dynamics
Xiaohong Yang, Dian Teguh, Jian-Ping Wu, Bo He, Thomas Brett Kirk, Shengnan Qin, Siming Li, Honghui Chen, Wei Xue, Benjamin Ng, Shek Man Chim, Jennifer Tickner, Jiake Xu
INTRODUCTION: Structural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-δ) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known. METHODS: Histological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone-cartilage interface in PKC-δ knockout (KO) mice...
2015: Arthritis Research & Therapy
Mark J Mondrinos, Linda C Knight, Paul A Kennedy, Jichuan Wu, Matthew Kauffman, Sandy T Baker, Marla R Wolfson, Laurie E Kilpatrick
Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)-conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy...
October 2015: Journal of Pharmacology and Experimental Therapeutics
Wei Ma, Claudia Baumann, Maria M Viveiros
This study tested the function of protein kinase C delta (PKCδ) during fertilization and embryonic development using gene-knockout (Prkcd(-/-)) mice. Fertility analysis revealed that Prkcd(-/-) mating pairs produce significantly fewer pups per litter than wild-type pairs (P < 0.05), and exhibit a high incidence of embryonic loss post-implantation. Both Prkcd(-/-) male as well as Prkcd(-/-) female mice mated to Prkcd(+/+) controls also showed reduced litter sizes, with a selective loss of Prkcd-null pups...
October 2015: Molecular Reproduction and Development
Laura Díaz, Marta Martínez-Bonet, Javier Sánchez, Alejandra Fernández-Pineda, José Luis Jiménez, Eduardo Muñoz, Santiago Moreno, Susana Álvarez, Ma Ángeles Muñoz-Fernández
Multiple studies have shown that HIV-1 patients may develop virus reservoirs that impede eradication; these reservoirs include the central nervous system (CNS). Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. To broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as a latent HIV-1 activator. We used primary astrocytes, NHA cells, and astrocytoma cells U-87...
2015: Scientific Reports
Ying He, Zaijie Jim Wang
As one of the most effective and frequently used chemotherapeutic agents, paclitaxel produces peripheral neuropathy (paclitaxel-induced peripheral neuropathy or PIPN) that negatively affects chemotherapy and persists after cancer therapy. The mechanisms underlying this dose-limiting side effect remain to be fully elucidated. This study aimed to investigate the role of nociceptor protein kinase C (PKC) isoforms in PIPN. Employing multiple complementary approaches, we have identified a subset of PKC isoforms, namely βII, δ, and ϵ, were activated by paclitaxel in the isolated primary afferent sensory neurons...
March 18, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Thianzhou Zhang, Philip Sell, Ursula Braun, Michael Leitges
In this study, we used gene targeting in mice to identify the in vivo functions of PKD1. In addition to phenotypically characterizing the resulting knock-out animals, we also used mouse embryonic fibroblasts to investigate the associated signaling pathways in detail. This study is the first to use genetic deletion to reveal that PKD1 is a key regulator involved in determining the threshold of mitochondrial depolarization that leads to the production of reactive oxygen species. In addition, we also provide clear evidence that PKCδ is upstream of PKD1 in this process and acts as the activating kinase of PKD1...
April 17, 2015: Journal of Biological Chemistry
Jianli Gong, Yongneng Yao, Pingbo Zhang, Barath Udayasuryan, Elena V Komissarova, Ju Chen, Sivaraj Sivaramakrishnan, Jennifer E Van Eyk, Susan F Steinberg
The diverse roles of protein kinase C-δ (PKCδ) in cellular growth, survival, and injury have been attributed to stimulus-specific differences in PKCδ signaling responses. PKCδ exerts membrane-delimited actions in cells activated by agonists that stimulate phosphoinositide hydrolysis. PKCδ is released from membranes as a Tyr(313)-phosphorylated enzyme that displays a high level of lipid-independent activity and altered substrate specificity during oxidative stress. This study identifies an interaction between PKCδ's Tyr(313)-phosphorylated hinge region and its phosphotyrosine-binding C2 domain that controls PKCδ's enzymology indirectly by decreasing phosphorylation in the kinase domain ATP-positioning loop at Ser(359)...
May 2015: Molecular and Cellular Biology
Yuan Zhang, Hua Li, Yicheng Pu, Shan Gong, Chunfeng Liu, Xinghong Jiang, Jin Tao
Although melatonin receptors are widely expressed in the mammalian central nervous system and peripheral tissues, there are limited data regarding the functions of melatonin in cerebellar Purkinje cells. Here, we identified a novel functional role of melatonin in modulating P-type Ca(2+) channels and action-potential firing in rat Purkinje neurons. Melatonin at 0.1 μm reversibly decreased peak currents (I(Ba)) by 32.9%. This effect was melatonin receptor 1 (MT(R1)) dependent and was associated with a hyperpolarizing shift in the voltage dependence of inactivation...
April 2015: Journal of Pineal Research
Udayakumar Karunakaran, Si Jun Park, Do Youn Jun, Taebo Sim, Keun-Gyu Park, Myoung Ok Kim, In Kyu Lee
GNF-2 and GNF-5 are members of a new class of non-receptor tyrosine kinases inhibitors that possess excellent selectivity towards imatinib-resistant mutations found in chronic myeloid leukemia patients. On the other hand recent reports implicate abnormal tyrosine kinase signaling in β-cell death in Type I and Type II diabetes. In this work we determined the effects of GNF-2, GNF-5 on pancreatic β-cell death caused by streptozotocin (STZ). STZ treatment causes apoptosis of INS-1 cells by activation of intracellular ROS, c-jun N-terminal kinase (JNK), caspase 3, and caspase 3-dependent activation of protein kinase C delta (PKCδ)...
June 2015: Cellular Signalling
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"