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Pkc theta

Gamal Badr, Halise Inci Gul, Cem Yamali, Amal A M Mohamed, Badr M Badr, Mustafa Gul, Ahmad Abo Markeb, Nagwa Abo El-Maali
Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10)...
March 7, 2018: Bioorganic Chemistry
Agnes Czikora, Satyabrata Pany, Youngki You, Amandeep S Saini, Nancy E Lewin, Gary A Mitchell, Adelle Abramovitz, Noemi Kedei, Peter M Blumberg, Joydip Das
The PKC isozymes represent the most prominent family of signaling proteins mediating response to the ubiquitous second messenger diacylglycerol. Among them, PKCθ is critically involved in T-cell activation. Whereas all the other conventional and novel PKC isoforms have twin C1 domains with potent binding activity for phorbol esters, in PKCθ only the C1b domain possesses potent binding activity, with little or no activity reported for the C1a domain. In order to better understand the structural basis accounting for the very weak ligand binding of the PKCθ C1a domain, we assessed the effect on ligand binding of twelve amino acid residues which differed between the C1a and C1b domains of PKCθ...
January 6, 2018: Biochimica et Biophysica Acta
T Boulding, R D McCuaig, A Tan, K Hardy, F Wu, J Dunn, M Kalimutho, C R Sutton, J K Forwood, A G Bert, G J Goodall, L Malik, D Yip, J E Dahlstrom, A Zafar, K K Khanna, S Rao
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs...
January 8, 2018: Scientific Reports
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
Gabriella Dobrowolny, Martina Martini, Bianca Maria Scicchitano, Vanina Romanello, Simona Boncompagni, Carmine Nicoletti, Laura Pietrangelo, Simone De Panfilis, Angela Catizone, Marina Bouche, Marco Sandri, Rudiger Rudolf, Feliciano Protasi, Antonio Musaro
Aim Neuromuscular junction (NMJ) represents the morpho-functional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and Amyotrophic Lateral Sclerosis (ALS), display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Results Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1G93A in transgenic MLC/SOD1G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of Acetylcholine Receptor (AChR), and NMJ dismantlement...
September 20, 2017: Antioxidants & Redox Signaling
Giulia M Camerino, Olimpia Musumeci, Elena Conte, Kejla Musaraj, Adriano Fonzino, Emanuele Barca, Marco Marino, Carmelo Rodolico, Domenico Tricarico, Claudia Camerino, Maria R Carratù, Jean-François Desaphy, Annamaria De Luca, Antonio Toscano, Sabata Pierno
Statin therapy may induce skeletal muscle damage ranging from myalgia to severe rhabdomyolysis. Our previous preclinical studies showed that statin treatment in rats involves the reduction of skeletal muscle ClC-1 chloride channel expression and related chloride conductance (gCl). An increase of the activity of protein kinase C theta (PKC theta) isoform, able to inactivate ClC-1, may contribute to destabilize sarcolemma excitability. These effects can be detrimental for muscle function leading to drug-induced myopathy...
2017: Frontiers in Pharmacology
Kerstin Siegmund, Nikolaus Thuille, Katarzyna Wachowicz, Natascha Hermann-Kleiter, Gottfried Baier
The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay...
2017: PloS One
Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, Denise Soutar, Isabel Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation...
July 2017: Immunology and Cell Biology
Jung-Ah Kang, Hyunwoo Choi, Taewoo Yang, Steve K Cho, Zee-Yong Park, Sung-Gyoo Park
PDK1 is essential for T cell receptor (TCR)-mediated activation of NF-κB, and PDK1-induced phosphorylation of PKCθ is important for TCR-induced NF-κB activation. However, inverse regulation of PDK1 by PKCθ during T cell activation has not been investigated. In this study, we found that PKCθ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type PKCθ or of kinase-inactive form of PKCθ revealed that PKCθ induced phosphorylation of human PDK1 at Ser-64...
January 2017: Molecules and Cells
Pei Wu, Yang Liu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
The liver and intestine are susceptible to the oxidative damage which could result in several diseases. Choline deficiency induced oxidative damage in rat liver cells. Thus, this study aimed to investigate the potential molecular mechanisms responsible for choline deficiency-induced oxidative damage. Juvenile Jian carp were fed diets differing in choline content [165 (deficient group), 310, 607, 896, 1167 and 1820 mg/kg diet] respectively for 65 days. Oxidative damage, antioxidant enzyme activities and related gene expressions in the hepatopancreas and intestine were measured...
2017: PloS One
Maria Julia Marques
No abstract text is available yet for this article.
February 2017: EBioMedicine
Mateus F Alves, Marcus T Scotti, Luciana Scotti, Francisco Jaime Bezerra Mendonça, José M B Filho, Sílvia A L de Melo, Sócrates G Dos Santos, Margareth de F F M Diniz
The genus Cissampelos comprises of 21 species which have a wide global distribution and various pharmacological activities such as analgesic and antipyretic, antiinflammatory, anti-allergic, bronchodilation, and immunomodulation among others. Several compounds, mainly alkaloids with differing biological activities have been isolated from this genus. We will highlight antipyretic activities, anti-inflammatory, antiallergic, bronchodilatory, and immunomodulatory activities. In addition, we applied ligand-based-virtual screening associated with structure-based-virtual screening of a small dataset of 63 secondary metabolites from the Cissampelos genus of an in-house data bank, in order to select compounds with potential anti-inflammatory activity...
2017: Current Medicinal Chemistry
A Chen, W W Hu, X L Jiang, M Potegal, H Li
The roles of group I metabotropic glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) and mGluR5, in regulating synaptic plasticity and metaplasticity in the basolateral amygdala (BLA) remain unclear. The present study examined mGluR1- and mGluR5-mediated synaptic plasticity in the BLA and their respective signaling mechanisms. Bath application of the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG) (20 μM), directly suppressed basal fEPSPs (84.5 ± 6.3% of the baseline). The suppressive effect persisted for at least 30 min after washout; it was abolished by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) but was unaffected by the mGluR5 antagonist 2-methyl-6- (phenylethynyl)-pyridine (MPEP)...
February 2017: Psychopharmacology
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response...
May 2017: Journal of Allergy and Clinical Immunology
Jessica Byerly, Gwyneth Halstead-Nussloch, Koichi Ito, Igor Katsyv, Hanna Y Irie
BACKGROUND: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells...
September 23, 2016: Breast Cancer Research: BCR
Cheng-Yu Chen, Chen-Ming Su, Chin-Jung Hsu, Chien-Chung Huang, Shih-Wei Wang, Shih-Chia Liu, Wei-Cheng Chen, Lih-Jyh Fuh, Chih-Hsin Tang
Angiogenesis is the formation of new capillaries from preexisting vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls...
January 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Christa Pfeifhofer-Obermair, Karin Albrecht-Schgoer, Sebastian Peer, Manfred Nairz, Kerstin Siegmund, Victoria Klepsch, David Haschka, Nikolaus Thuille, Natascha Hermann-Kleiter, Thomas Gruber, Günter Weiss, Gottfried Baier
BACKGROUND: The serine/threonine protein kinase C (PKC) theta has been firmly implicated in T cell-mediated immunity. Because its role in macrophages has remained undefined, we employed PKCtheta-deficient (PKCtheta (-/-)) mice in order to investigate if PKCtheta plays a role in macrophage-mediated immune responses during bacterial infections. RESULTS: Our results demonstrate that PKCtheta plays an important role in host defense against the Gram-negative, intracellular bacterium Salmonella typhimurium, as reflected both by markedly decreased survival and a significantly enhanced number of bacteria in spleen and liver of PKCtheta (-/-) mice, when compared to wild-type mice...
July 28, 2016: Cell Communication and Signaling: CCS
Purushotham Kkrishnappa, Eu Jhin Loh, Ibtisam Binti Mohamad, Mahadevan Deva Tata, Meenakshi Akhilesh, Kandasami Palayan
PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia. MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Deebika Balu, John R Larson, Jennifer V Schmidt, David Wirtshafter, Aleksey Yevtodiyenko, John P Leonard
Activity-dependent plasticity in NMDA receptor-containing synapses can be regulated by phosphorylation of serines and tyrosines in the C-terminal domain of the receptor subunits by various kinases. We have previously identified S1291/S1312 as important sites for PKC phosphorylation; while Y1292/Y1312 are the sites indirectly phosphorylated by PKC via Src kinase. In the oocyte expression system, mutation of those Serine sites to Alanine (that cannot be phosphorylated) in the GluN2A subunit, resulted in a decreased PKC stimulated current enhancement through the receptors compared to wild-type NMDA receptors...
September 1, 2016: Brain Research
Jasmine Li, Kristine Hardy, Chan Phetsouphanh, Wen Juan Tu, Elissa L Sutcliffe, Robert McCuaig, Christopher R Sutton, Anjum Zafar, C Mee Ling Munier, John J Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek Siew Lim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J Milburn, Jenny Dunn, Marco G Casarotto, Stephen J Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao
Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation...
June 15, 2016: Journal of Cell Science
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