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https://www.readbyqxmd.com/read/27927752/vesicular-ptdins-3-4-5-p3-and-rab-7-are-key-effectors-of-zygote-nuclear-membrane-fusion
#1
Marta G Lete, Richard D Byrne, Alicia Alonso, Dominic Poccia, Banafshé Larijani
Regulation of nuclear envelope (NE) dynamics is an important example of the universal phenomena of membrane fusion. The signalling molecules involved in nuclear membrane fusion may also be conserved in the formation of both pronuclear and zygote NEs in the fertilised egg. Here, we determine that Class I PI3-kinases are needed for in vitro nuclear envelope formation. We show that, in vivo, PtdIns(3,4,5)P3 is transiently located in vesicles around the male pronucleus at the time of nuclear envelope formation and around male and female pronuclei prior to membrane fusion...
December 7, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27926856/insulin-dependent-activation-of-mch-neurons-impairs-locomotor-activity-and-insulin-sensitivity-in-obesity
#2
A Christine Hausen, Johan Ruud, Hong Jiang, Simon Hess, Hristo Varbanov, Peter Kloppenburg, Jens C Brüning
Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27923617/novel-pyrazolo-1-5-a-pyridines-with-improved-aqueous-solubility-as-p110%C3%AE-selective-pi3-kinase-inhibitors
#3
Jackie D Kendall, Anna C Giddens, Kit Yee Tsang, Elaine S Marshall, Claire L Lill, Woo-Jeong Lee, Sharada Kolekar, Mindy Chao, Alisha Malik, Shuqiao Yu, Claire Chaussade, Christina Buchanan, Stephen M F Jamieson, Gordon W Rewcastle, Bruce C Baguley, William A Denny, Peter R Shepherd
As part of our investigation into pyrazolo[1,5-a]pyridines as novel p110α selective PI3 kinase inhibitors, we report a range of analogues with improved aqueous solubility by the addition of a basic amine. The compounds demonstrated comparable p110α potency and selectivity to earlier compounds but with up to 1000× greater aqueous solubility, as the hydrochloride salts. The compounds also displayed good activity in a cellular assay of PI3 kinase activity.
November 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27919679/regulation-of-protein-kinase-c-epsilon-and-its-age-dependence
#4
Chen Kang, Jingping Qin, Wil Osei, Keli Hu
Protein kinase C (PKC) is an important mediator in the cardioprotection of ischemic preconditioning and has been shown to translocate to mitochondria upon activation. However, little is known about the cellular signaling underlying the translocation of PKC isoforms to mitochondria and its age-dependence. The present study aimed to explore whether adenosine-induced translocation of PKCε to mitochondria is mediated by caveolin-3 and/or adenosine A2B receptor/PI3 kinase mediated signaling, and whether the mitochondrial targeting of PKCε is age-related...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27918554/asic1a-mediates-the-drug-resistance-of-human-hepatocellular-carcinoma-via-the-ca-2-pi3-kinase-akt-signaling-pathway
#5
Yihao Zhang, Ting Zhang, Chao Wu, Quan Xia, Dujuan Xu
Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H(+)-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27918278/pi3-kinase-cascade-has-a-differential-role-in-acquisition-and-extinction-of-conditioned-fear-memory-in-juvenile-and-adult-rats
#6
Ilana Slouzkey, Mouna Maroun
The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory...
December 2016: Learning & Memory
https://www.readbyqxmd.com/read/27897192/pi3-kinase-inhibition-improves-vascular-malformations-in-mouse-models-of-hereditary-haemorrhagic-telangiectasia
#7
Roxana Ola, Alexandre Dubrac, Jinah Han, Feng Zhang, Jennifer S Fang, Bruno Larrivée, Monica Lee, Ana A Urarte, Jan R Kraehling, Gael Genet, Karen K Hirschi, William C Sessa, Francesc V Canals, Mariona Graupera, Minhong Yan, Lawrence H Young, Paul S Oh, Anne Eichmann
Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27896643/a-novel-signaling-role-for-mir-451-in-esophageal-tumor-microenvironment-and-its-contribution-to-tumor-progression
#8
S Khazaei, N Nouraee, A Moradi, S J Mowla
OBJECTIVE: We evaluated miR-451 expression in serum and tissue samples of esophageal squamous cell carcinoma (ESCC) patients. Then, we examined a secretory role of miR-451 in esophageal tumor microenvironment. METHODS: miR-451 expression was evaluated in 39 serum samples from esophageal SCC patients compared to 39 normal individuals as well as 26 pairs of fresh-frozen tumor and adjacent normal tissues from patients with ESCC, using qRT-PCR. In a co-culture system of human normal fibroblasts (HFSF-PI3) and esophageal cancer cell line (KYSE-30), we evaluated exosomal miR-451 secretion into the conditioned medium (CM) of both cell lines...
November 28, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27885699/strains-of-group-b-streptococci-from-septic-patients-induce-platelet-activation-via-toll-like-receptor-2
#9
Xiaoyan Liu, Hongyun Liu, Xianming Luo, Ping Zhang, Yanmin Gao, Shuangfeng Xie, Kang Xu, Jianxing Chang, Liping Ma
Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially in newborns and pregnant women. Patients suffering from sepsis often display low platelet counts, characterized by thrombocytopenia, because of platelet activation. In the present study, the roles of six GBS strains from septic patients in platelet aggregation, as well as the underlying mechanisms, were investigated. Incubation of platelets with three of the strains induced platelet aggregation, increased the secretion of cellular adhesin molecule CD62P and activation of GPIIb/IIIa...
November 25, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27885462/the-cytoprotective-effect-of-rumex-aquaticus-herba-extract-against-hydrogen-peroxide-induced-oxidative-stress-in-ags-cells
#10
Eun Jeong Cho, Seung In Um, Jeong Hoon Han, Byeonghee Kim, Sang Beom Han, Ji Hoon Jeong, Hak Rim Kim, Inkyeom Kim, Wan Kyun Whang, Eunhwa Lee, Uy Dong Sohn
The Rumex Aquaticus Herba extract containing quercetin-3-β-D-glucuronopyranoside (ECQ) has been reported to exhibit various pharmacological activities, including anti-inflammatory and anti-oxidative effects. This plant has been traditionally used for the treatment of diarrhea, disinfestation, edema and jaundice, and as an antipyretic drug. The aim of the present study was to investigate the ability of ECQ to protect against oxidative damage and to determine its signaling mechanism in AGS cells. The protein expressions of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were measured by Western blots...
November 24, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27882154/kai-xin-san-a-traditional-chinese-medicine-formulation-exerts-antidepressive-and-neuroprotective-effects-by-promoting-pcreb-upstream-pathways
#11
Xian-Zhe Dong, Dong-Xiao Wang, Bing-Ying Yu, Ping Liu, Yuan Hu
Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27875972/the-role-of-chinese-herbal-medicines-and-bioactive-ingredients-targeting-myocardial-kca-and-katp-channels-in-cardiovascular-diseases
#12
Yan Dong, Pengqian Wang, Xue Feng, Bing Li, Zhong Wang, Haixia Li
Cardiovascular disorders are the most common diseases all over the world, which have limitations in the current treatment strategies. As two subtypes of potassium channel, KCa and KATP ion channels are playing important roles in the occurrence and development of cardiovascular diseases. KCa by activating the signal pathway of c-Src/PI3-kinase/Akt-dependent or eNOS-NO-cGMP affects the function of vascular endothelial cell, while KATP acting as medium combines the cell electrical activity and energy metabolism...
November 22, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27871300/pi3-kinase-pathway-regulated-mirnome-in-glioblastoma-identification-of-mir-326-as-a-tumour-suppressor-mirna
#13
Zahid Nawaz, Vikas Patil, Yashna Paul, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram
BACKGROUND: Glioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored...
November 21, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27866373/involvement-of-gsk-3%C3%AE-phosphorylation-through-pi3-k-akt-in-cerebral-ischemia-induced-neurogenesis-in-rats
#14
Keishi Kisoh, Hideki Hayashi, Tsuyoshi Itoh, Mayumi Asada, Miho Arai, Bo Yuan, Kouichi Tanonaka, Norio Takagi
Glycogen synthase kinase (GSK)-3β, which is abundantly expressed in the central nervous system, regulates various cellular processes including gene expression, cell proliferation, and differentiation. However, involvement of GSK-3β in cerebral ischemia-induced endogenous neurogenesis is not yet fully understood. Appropriate strategies to prevent ischemic cell damage and subsequent severe sequelae are needed. The purpose of the present study was to determine the relationship between pathophysiological alteration of the GSK-3β signaling pathway and cerebral ischemia-induced endogenous neurogenesis in rats...
November 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27866306/low-dose-of-bisphenol-a-activates-nf-%C3%AE%C2%BAb-il-6-signals-to-increase-malignancy-of-neuroblastoma-cells
#15
Shunjun Xiong, Yanjun Wang, Huijuan Li, Xiaofang Zhang
Bisphenol A (BPA) can accumulate in the human body and promote the progression of various cancers. However, its role in the development of neuroblastoma (NB) is largely unknown. Our present study revealed that nanomolar concentrations of BPA can significantly increase the proliferation, migration and invasion of NB SH-SY5Y and SiMa cells, further evidenced by the upregulation of human proliferating cell nuclear antigen, Bcl-2, vimentin and fibronectin. Real-time PCR and ELISA results suggested that nanomolar BPA can increase the expression of interleukin-6 (IL-6), but had no effect on the expression of IL-2, IL-8, IL-10 or IL-12...
November 19, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27856419/neuropeptide-y-npy-promotes-inflammation-induced-tumorigenesis-by-enhancing-epithelial-cell-proliferation
#16
Sabrina Jeppsson, Shanthi Srinivasan, Bindu Chandrasekharan
We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSSn) was used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout (NPY(-/-)) mice...
November 17, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27856280/microcystin-lr-promotes-epithelial-mesenchymal-transition-in-colorectal-cancer-cells-through-pi3-k-akt-and-smad2
#17
Yan Ren, Mengli Yang, Meng Chen, Qiangqiang Zhu, Lihua Zhou, Wei Qin, Ting Wang
Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer cells. However, the roles of MC-LR in regulating epithelial-mesenchymal transition (EMT) in colorectal cancer cells remain unknown. In our study, we observed that MC-LR treatment decreased epithelial marker E-cadherin expression and up-regulated the levels of mesenchymal markers Vimentin and Snail in colorectal cancer cells...
November 14, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#18
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27852846/a-transformation-defective-polyomavirus-middle-t-antigen-with-a-novel-defect-in-pi3-kinase-signaling
#19
Deborah Denis, Cecile Rouleau, Brian S Schaffhausen
: Middle T antigen (MT), the principal oncoprotein of murine polyomavirus, transforms by association with cellular proteins. PP2A, YAP, Src family tyrosine kinases, Shc, phosphoinositide-3-kinase (PI3K) and PLCγ1 have all been implicated in MT transformation. Mutant dl1015, deleting residues 338-347 in the C-terminal region, has been an enigma, because the basis for its transformation defect has not been apparent. This work probes the dl1015 region of MT. Because the region is proline rich, the hypothesis that it targets SH3 domains was tested, but mutation of the putative SH3 binding motif did not affect transformation...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27852227/long-lasting-reduction-in-clonogenic-potential-of-colorectal-cancer-cells-by-sequential-treatments-with-5-azanucleosides-and-topoisomerase-inhibitors
#20
Alicja Pawlak, Ewa Ziolo, Anna Fiedorowicz, Klaudyna Fidyt, Leon Strzadala, Wojciech Kalas
BACKGROUND: The currently approved therapies fail in a substantial number of colorectal cancer (CRC) patients due to the molecular heterogeneity of CRC, hence new efficient drug combinations are urgently needed. Emerging data indicate that 5-azanucleosides are able to sensitize cancer cells to the standard chemotherapeutic agents and contribute to overcoming intrinsic or acquired chemoresistance. METHODS: CRC cells with different genetic backgrounds (HCT116, DLD-1, HT-29) were sequentially treated with 5-azanucleosides and topoisomerase inhibitors...
November 16, 2016: BMC Cancer
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