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https://www.readbyqxmd.com/read/27893829/sansevieria-roxburghiana-schult-schult-f-family-asparagaceae-attenuates-type-2-diabetes-and-its-associated-cardiomyopathy
#1
Niloy Bhattacharjee, Ritu Khanra, Tarun K Dua, Susmita Das, Bratati De, M Zia-Ul-Haq, Vincenzo De Feo, Saikat Dewanjee
BACKGROUND: Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. METHODS: SR was chemically characterized by GC-MS analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27882944/grk6-regulates-ros-response-and-maintains-hematopoietic-stem-cell-self-renewal
#2
Qiumin Le, Wenqing Yao, Yuejun Chen, Biao Yan, Cao Liu, Man Yuan, Yuqing Zhou, Lan Ma
G protein-coupled receptor kinases (GRKs) are critically involved in immune response through regulation of cytokine receptors in mature leukocytes, but their role in hematopoiesis is largely unknown. Here, we demonstrate that GRK6 knockout (GRK6(-/-)) mice exhibit lymphocytopenia, loss of the hematopoietic stem cell (HSC) and multiple progenitor populations. GRK6 deficiency leads to compromised lymphoid differentiation, largely owing to the impairment of HSC self-renewal. Transcriptome and proteomic analysis suggest that GRK6 is involved in reactive oxygen species signaling...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27875301/an-intrinsically-disordered-aplf-links-ku-dna-pkcs-and-xrcc4-dna-ligase-iv-in-an-extended-flexible-non-homologous-end-joining-complex
#3
Michal Hammel, Yaping Yu, Sarvan Kumar Radhakrishnan, Chirayu Chokshi, Miaw-Sheue Tsai, Yoshihiro Matsumoto, Monica Kuzdovich, Soumya G Remesh, Shujuan Fang, Alan E Tomkinson, Susan P Lees-Miller, John A Tainer
DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF) and XRCC4 (X4)-DNA ligase IV (L4). In addition, Ku interacts with accessory factors such as Aprataxin and Polynucleotide kinase/phosphatase-Like Factor (APLF), yet how these factors interact to tether, process and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27866196/down-regulation-of-protein-kinase-c-%C3%AE%C2%B5-by-prolonged-incubation-with-pma-inhibits-the-proliferation-of-vascular-smooth-muscle-cells
#4
Huixuan Zhou, Yan Wang, Quanhong Zhou, Bin Wu, Aizhong Wang, Wei Jiang, Li Wang
BACKGROUND/AIMS: Phorbol myristate acetate (PMA) exerts a pleiotropic effect on the growth and differentiation of various cells. Protein kinase Cs (PKCs) plays a central role in mediating the effects of PMA on cells. The present study investigated whether the down-regulation of protein kinase C-ε (PKC-ε) is involved in the inhibition of vascular smooth muscle cell (VSMC) proliferation caused by prolonged PMA incubation. METHODS: Using cell counting, Cell Counting Kit-8 (CCK-8) and EdU incorporation assay on VSMCs, we evaluated the inhibitory effects of prolonged incubation of PMA, of lentiviruses carrying the short-hairpin RNAs (shRNA) of PKC-ε and of the PKC-ε inhibitor peptide on the proliferation and viability of cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27834678/receptor-species-dependent-desensitization-controls-kcnq1-kcne1-k-channels-as-downstream-effectors-of-gq-protein-coupled-receptors
#5
Marie-Cécile Kienitz, Dilyana Vladimirova, Christian Müller, Lutz Pott, Andreas Rinne
Activation of Gq protein-coupled receptors (GqPCRs) might induce divergent cellular responses, related to receptor-specific activation of different branches of the Gq-signaling pathway. Receptor-specific desensitization provides a mechanism of effector modulation by restricting the spatiotemporal activation of signaling components downstream of Gq We quantified signaling events downstream to GqPCR activation with Foerster resonance energy transfer (FRET)-based biosensors in CHO and HEK 293 cells. KCNQ1/KCNE1 channels (IKs) were measured as a functional readout of receptor-specific activation...
November 10, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27830506/vitamin-a-as-pkc-co-factor-and-regulator-of-mitochondrial-energetics
#6
Ulrich Hammerling
For the past century, vitamin A has been considered to serve as a precursor for retinoids that facilitate vision or as a precursor for retinoic acid (RA), a signaling molecule that modulates gene expression. However, vitamin A circulates in plasma at levels that far exceed the amount needed for vision or the synthesis of nanomolar levels of RA, and this suggests that vitamin A alcohol (i.e. retinol) may possess additional biological activity. We have pursued this question for the last 20 years, and in this chapter, we unfold the story of our quest and the data that support a novel and distinct role for vitamin A (alcohol) action...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27829224/inhibition-of-chk1-with-the-small-molecule-inhibitor-v158411-induces-dna-damage-and-cell-death-in-an-unperturbed-s-phase
#7
Joanne Wayne, Teresa Brooks, Andrew J Massey
Chk1 kinase is a critical component of the DNA damage response checkpoint and Chk1 inhibitors are currently under clinical investigation. Chk1 suppresses oncogene-induced replication stress with Chk1 inhibitors demonstrating activity as a monotherapy in numerous cancer types. Understanding the mechanism by which Chk1 inhibitors induce DNA damage and cancer cell death is essential for their future clinical development. Here we characterize the mechanism by which the novel Chk1 inhibitor (V158411) increased DNA damage and cell death in models of human cancer...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27824138/b7-h1-antibodies-lose-antitumor-activity-due-to-activation-of-p38-mapk-that-leads-to-apoptosis-of-tumor-reactive-cd8-t-cells
#8
Xin Liu, Xiaosheng Wu, Siyu Cao, Susan M Harrington, Peng Yin, Aaron S Mansfield, Haidong Dong
B7-H1 (aka PD-L1) blocking antibodies have been used in treatment of human cancers through blocking B7-H1 expressed by tumor cells; however, their impact on B7-H1 expressing tumor-reactive CD8(+) T cells is still unknown. Here, we report that tumor-reactive CD8(+) T cells expressing B7-H1 are functional effector cells. In contrast to normal B7-H1 blocking antibody, B7-H1 antibodies capable of activating p38 MAPK lose their antitumor activity by deleting B7-H1(+) tumor-reactive CD8(+) T cells via p38 MAPK pathway...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27810601/differential-roles-of-pkc-isoforms-pkcs-and-ca-2-in-gnrh-and-phorbol-12-myristate-13-acetate-pma-stimulation-of-p38mapk-phosphorylation-in-immortalized-gonadotrope-cells
#9
Shany Mugami, Shani Kravchook, Liat Rahamim-Ben Navi, Rony Seger, Zvi Naor
We examined the role of PKCs and Ca(2+) in GnRH-stimulated p38MAPK phosphorylation in the gonadotrope derived αT3-1 and LβT2 cell lines. GnRH induced a slow and rapid increase in p38MAPK phosphorylation in αT3-1 and LβT2 cells respectively, while PMA gave a slow response. The use of dominant negatives for PKCs and peptide inhibitors for the receptors for activated C kinase (RACKs), has revealed differential role for PKCα, PKCβII, PKCδ and PKCε in p38MAPK phosphorylation in a ligand-and cell context-dependent manner...
November 1, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27789167/dna-pkcs-a-promising-therapeutic-target-in-human-hepatocellular-carcinoma
#10
REVIEW
Rosa M Pascale, Christy Joseph, Gavinella Latte, Matthias Evert, Francesco Feo, Diego F Calvisi
Hepatocellular carcinoma (HCC) is a frequent and deadly disease worldwide. The absence of effective therapies when the tumor is surgically unresectable leads to an extremely poor outcome of HCC patients. Thus, it is mandatory to elucidate the molecular pathogenesis of HCC in order to develop novel therapeutic strategies against this pernicious tumor. Mounting evidence indicates that suppression of the DNA damage response machinery might be deleterious for the survival and growth of the tumor cells. In particular, DNA dependent protein kinase catalytic subunit (DNA-PKcs), a major player in the non-homologous end-joining (NHEJ) repair process, seems to represent a valuable target for innovative anti-neoplastic therapies in cancer...
October 15, 2016: DNA Repair
https://www.readbyqxmd.com/read/27788957/targeting-phosphatidylinositol-4-kinase-iii%C3%AE-for-radiosensitization-a-potential-model-of-drug-repositioning-using-an-anti-hepatitis-c-viral-agent
#11
Jeanny Kwon, Dan Hyo Kim, Ji Min Park, Young Hee Park, Yeo Hyun Hwang, Hong-Gyun Wu, Kyung Hwan Shin, In Ah Kim
PURPOSE: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti-hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. METHODS AND MATERIALS: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed...
November 15, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27784455/-effects-and-its-mechanism-of-nimotuzumab-on-radiosensitivity-of-esophageal-carcinoma-eca-109-and-te-13-cell-lines
#12
J Wang, W Wang, Y Guo, S W Jing, K Shang, M C Miao, J Wang, Y J Wu, L N Liu, J M Yu
Objective: To investigate the effects of nimotuzumab on radiosensitivity of ECA-109 and TE-13 esophageal carcinoma cell lines and explore its possible mechanism. Methods: The ECA-109 and TE-13 cells were divided into control group, irradiation group, medicine group, and combined group (irradiation + medicine). In the combined group, ECA-109 and TE-13 cells were treated with nimotuzumab for 24 h before irradiation, and the cells were collected 2 h after irradiation. The radiosensitizing effects of nimotuzumab on ECA-109 and TE-13 cells were evaluated by clone formation assay...
October 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27765919/zoledronic-acid-is-an-effective-radiosensitizer-in-the-treatment-of-osteosarcoma
#13
Eun Ho Kim, Mi-Sook Kim, Kyung-Hee Lee, Jae-Soo Koh, Won-Gyun Jung, Chang-Bae Kong
To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27765904/identification-of-dna-pkcs-as-a-primary-resistance-factor-of-salinomycin-in-osteosarcoma-cells
#14
Yun-Fang Zhen, Song-Tao Li, Yun-Rong Zhu, Xiao-Dong Wang, Xiao-Zhong Zhou, Lun-Qing Zhu
Malignant osteosarcoma (OS) is still a deadly disease for many affected patients. The search for the novel anti-OS agent is extremely urgent and important. Our previous study has proposed that salinomycin is a novel anti-OS agent. Here we characterized DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a primary salinomycin resistance factor in OS cells. DNA-PKcs inhibitors (NU7026, NU7441 and LY294002) or DNA-PKcs shRNA knockdown dramatically potentiated salinomycin-induced death and apoptosis of OS cells (U2OS and MG-63 lines)...
October 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27760826/pleckstrin-homology-ph-domain-leucine-rich-repeat-protein-phosphatase-controls-cell-polarity-by-negatively-regulating-the-activity-of-atypical-protein-kinase-c
#15
Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27741226/mechanistic-modelling-and-bayesian-inference-elucidates-the-variable-dynamics-of-double-strand-break-repair
#16
Mae L Woods, Chris P Barnes
DNA double-strand breaks are lesions that form during metabolism, DNA replication and exposure to mutagens. When a double-strand break occurs one of a number of repair mechanisms is recruited, all of which have differing propensities for mutational events. Despite DNA repair being of crucial importance, the relative contribution of these mechanisms and their regulatory interactions remain to be fully elucidated. Understanding these mutational processes will have a profound impact on our knowledge of genomic instability, with implications across health, disease and evolution...
October 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27733644/the-dna-damage-signaling-is-required-for-replication-of-the-hbov1-dna-in-dividing-hek293-cells
#17
Xuefeng Deng, Peng Xu, Wei Zou, Weiran Shen, Jianxin Peng, Kaiyu Liu, John F Engelhardt, Ziying Yan, Jianming Qiu
: Human bocavirus 1 (HBoV1), an emerging human pathogenic respiratory virus, is a member of the genus Bocaparvovirus of the Parvoviridae family. In human airway epithelia air-liquid interface (HAE-ALI) cultures, HBoV1 infection initiates a DNA damage response (DDR), activating all three phosphatidylinositol 3-kinase-related kinases (PI3KKs): ATM, ATR and DNA-PKcs. In this context, activation of PI3KKs is a requirement for amplification of the HBoV1 genome (PLoS Pathog., 2016; 12:e1005399), and HBoV1 replicates only in terminally differentiated, non-dividing cells...
October 12, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27731641/isolation-of-phorbol-esters-from-euphorbia-grandicornis-and-evaluation-of-protein-kinase-c-and-human-platelet-activating-effects-of-euphorbiaceae-diterpenes
#18
Ju-Ying Tsai, Dóra Rédei, Peter Forgo, Yu Li, Andrea Vasas, Judit Hohmann, Chin-Chung Wu
Human platelets contain conventional (α and β) and novel isoforms of PKC (δ and θ), and PKC activation can result in platelet aggregation and secretion reaction that are important for thrombus formation. Several tumor-promoting Euphorbiaceae diterpenes are known to act as direct activators of PKC, but many types of such diterpenes have not been studied as platelet stimulators. In the present study, two new and five known phorbol esters were isolated from Euphorbia grandicornis. Two of the isolated phorbol esters together with compounds representing ingenane, jatrophane, and myrsinane structural types were studied on PKC activation and platelet stimulation...
October 12, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27721000/effects-of-extremely-low-frequency-electromagnetic-field-and-cisplatin-on-mrna-levels-of-some-dna-repair-genes
#19
Fatemeh Sanie-Jahromi, Iraj Saadat, Mostafa Saadat
AIMS: It has been shown that exposure to extremely-low frequency (˂300Hz) oscillating electromagnetic field (EMF) can affect gene expression. The effects of different exposure patterns of 50-Hz EMF and co-treatment of EMF plus cisplatin (CDDP) on mRNA levels of seven genes involved in DNA repair pathways (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) were evaluated. MAIN METHODS: Two 50-Hz EMF intensities (0.25 and 0.50mT), three exposure patterns (5min field-on/5min field-off, 15min field-on/15min field-off, 30min field-on continuously) and two cell lines (MCF-7 and SH-SY5Y) were used...
October 6, 2016: Life Sciences
https://www.readbyqxmd.com/read/27717886/the-interplay-between-intracellular-progesterone-receptor-and-pkc-plays-a-key-role-in-migration-and-invasion-of-human-glioblastoma-cells
#20
Brenda Marquina-Sánchez, Jesús González-Jorge, Valeria Hansberg-Pastor, Talia Wegman-Ostrosky, Noemi Baranda-Ávila, Sonia Mejía-Pérez, Ignacio Camacho-Arroyo, Aliesha González-Arenas
Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are found overexpressed in grade IV human astrocytomas, also known as glioblastomas, which are the most frequent and aggressive brain tumors. In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation. We observed that PKC activation with tetradecanoylphorbol acetate (TPA) increases the migration and invasion capacity of two human glioblastoma derived human cell lines (U251 MG and U87) and that the treatment with the PR receptor antagonist RU486 blocks these processes...
October 4, 2016: Journal of Steroid Biochemistry and Molecular Biology
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