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https://www.readbyqxmd.com/read/29913143/lactate-enhanced-the-effect-of-parathyroid-hormone-on-osteoblast-differentiation-via-gpr81-pkc-akt-signaling
#1
Yu Wu, Miaomiao Wang, Kefan Zhang, Yingjiang Li, Manlin Xu, Shaidi Tang, Xiuxia Qu, Chunping Li
Osteoblast uses aerobic glycolysis to meet the metabolic needs in differentiation process. Lactate, the end product of glycolysis, presents in the environment with elevated PTH and osteoblast differentiation. Although previous findings showed that lactate promoted osteoblast differentiation, whether lactate affects PTH-mediated osteoblast differentiation is unclear. To investigate this, pre-osteoblast cell line MC3T3-E1 was treated PTH with or without physiological dose of lactate. Lactate increases ALP positive cell formation, increases ALP activity and expression of differentiation related markers, enriches the CREB transcriptional factor target genes in PTH treated cells...
June 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29908295/hyperglycaemic-impairment-of-par2-mediated-vasodilation-prevention-by-inhibition-of-aortic-endothelial-sodium-glucose-co-transporter-2-and-minimizing-oxidative-stress
#2
Mahmoud El-Daly, Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Sean Kang, Paul W M Fedak, Laurie A Alston, Simon A Hirota, Hong Ding, Chris R Triggle, Morley D Hollenberg
Hyperglycaemia is a major contributor to diabetic cardiovascular disease with hyperglycaemia-induced endothelial dysfunction recognized as the initiating cause. Coagulation pathway-regulated proteinase-activated receptors (PARs) that can regulate vascular tone in vivo cause eNOS-mediated endothelium-dependent vasodilation; but, the impact of hyperglycaemia on this vasodilatory action of PAR stimulation and the signalling pathways involved are unknown. We hypothesized that vascular sodium-glucose co-transporter 2 activity and hyperglycaemia-induced oxidative stress involving Src-kinase, EGF receptor-kinase, Rho-kinase and protein-kinase-C biochemical signalling pathways would compromise PAR2-mediated endothelium-dependent vasodilation...
June 13, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29903018/emerging-roles-and-regulation-of-mit-tfe-transcriptional-factors
#3
REVIEW
Min Yang, En Liu, Li Tang, Yuanyuan Lei, Xuemei Sun, Jiaxi Hu, Hui Dong, Shi-Ming Yang, Mingfa Gao, Bo Tang
The MiT/TFE transcription factors play a pivotal role in the regulation of autophagy and lysosomal biogenesis. The subcellular localization and activity of MiT/TFE proteins are primarily regulated through phosphorylation. And the phosphorylated protein is retained in the cytoplasm and subsequently translocates to the nucleus upon dephosphorylation, where it stimulates the expression of hundreds of genes, leading to lysosomal biogenesis and autophagy induction. The transcription factor-mediated lysosome-to-nucleus signaling can be directly controlled by several signaling molecules involved in the mTORC1, PKC, and AKT pathways...
June 15, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29901193/pioglitazone-restores-the-homocysteine%C3%A2-impaired-function-of-endothelial-progenitor-cells-via-the-inhibition-of-the-protein-kinase-c-nadph-oxidase-pathway
#4
Junhui Zhu, Yanbo Zhao, Lu Yu, Meihui Wang, Qinfeng Li, Shengjie Xu
Homocysteine (Hcy) has been shown to impair the migratory and adhesive activity of endothelial progenitor cells (EPCs). As a peroxisome proliferator‑activated receptor γ agonist, pioglitazone (PIO) has been predicted to regulate angiogenesis, and cell adhesion, migration and survival. The aim of the present study was to determine whether PIO could inhibit Hcy‑induced EPC dysfunctions such as impairments of cell migration and adhesion. EPC migration and adhesion were assayed using 8.0‑µm pore size Transwell membranes and fibronectin‑coated culture dishes, respectively...
June 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29900041/neurotensin-il-8-pathway-orchestrates-local-inflammatory-response-and-tumor-invasion-by-inducing-m2-polarization-of-tumor-associated-macrophages-and-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells
#5
Pei Xiao, Xinxin Long, Lijie Zhang, Yingnan Ye, Jincheng Guo, Pengpeng Liu, Rui Zhang, Junya Ning, Wenwen Yu, Feng Wei, Jinpu Yu
We previously demonstrated that neurotensin (NTS) induces local inflammation and promotes tumor invasion in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms are not clear. In this study, positive correlations between NTS and interleukin (IL)-8 were identified at both the mRNA and protein levels in 71 fresh HCC tissues and 100 paraffin-embedded HCC tissues. Furthermore, significant correlations were determined among the co-expression of NTS and IL-8, infiltration of inflammatory cells and enhanced epithelial-mesenchymal transition (EMT) of HCC cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899861/deregulation-of-calcium-homeostasis-in-bcr-abl-dependent-chronic-myeloid-leukemia
#6
Hélène Cabanas, Thomas Harnois, Christophe Magaud, Laëtitia Cousin, Bruno Constantin, Nicolas Bourmeyster, Nadine Déliot
Background: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the bcr-abl chimeric oncogene, encoding a 210 kDa protein with constitutive tyrosine kinase activity. In spite of the efficiency of tyrosine kinase inhibitors (TKI; Imatinib), other strategies are explored to eliminate CML leukemia stem cells, such as calcium pathways. Results: In this work, we showed that Store-Operated Calcium Entry (SOCE) and thrombin induced calcium influx were decreased in Bcr-Abl expressing 32d cells (32d-p210)...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899230/hydroxyl-group-and-vasorelaxant-effects-of-perillyl-alcohol-carveol-limonene-on-aorta-smooth-muscle-of-rats
#7
Ana Carolina Cardoso-Teixeira, Francisco Walber Ferreira-da-Silva, Dieniffer Peixoto-Neves, Klausen Oliveira-Abreu, Átila Pereira-Gonçalves, Andrelina Noronha Coelho-de-Souza, José Henrique Leal-Cardoso
The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory effect on the contraction induced by electromechanical and pharmacomechanical coupling. In the case of LM, but not CV and POH, this effect was influenced by preservation of the endothelium. POH and CV but not LM exhibited greater pharmacological potency on BayK-8644-induced contraction and on electromechanical coupling than on pharmacomechanical coupling...
June 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29897736/dexmedetomidine-an-alpha-2a-adrenergic-receptor-agonist-mitigates-experimental-autoimmune-encephalomyelitis-by-desensitization-of-cxcr7-in-microglia
#8
Yi Huang, Shite Hu, Yongliang Li, Dan Xue, Xiuguo Wu
In the autoimmune disease multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), characterized by an ascending paralysis that is characterized by extensive infiltration of the central nervous system by inflammatory cells. Although several studies to some extent uncover the cellular mechanisms of microglia that govern EAE pathogenesis, the molecular mechanisms that orchestrate microglia movement remain unknown and potential novel therapeutic strategies are still required...
June 13, 2018: Biochemistry
https://www.readbyqxmd.com/read/29897293/the-oxytocin-receptor-from-intracellular-signaling-to-behavior
#9
Benjamin Jurek, Inga D Neumann
The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1 , as listed in PubMed), which revealed central roles for OXT and its receptor (OXTR) in reproduction, and social and emotional behaviors in animal and human studies focusing on mental and physical health and disease. In this review, we discuss the mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OXTR-coupled signaling cascades, and their involvement in behavioral outcomes to assemble a comprehensive picture of the central and peripheral OXT system...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29894755/activation-of-bradykinin-b2-receptor-induced-the-inflammatory-responses-of-cytosolic-phospholipase-a-2-after-the-early-traumatic-brain-injury
#10
Honglu Chao, Yinlong Liu, Chao Lin, Xiupeng Xu, Zheng Li, Zhongyuan Bao, Liang Fan, Chao Tao, Lin Zhao, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
Phospholipase A2 is a known aggravator of inflammation and deteriorates neurological outcomes after traumatic brain injury (TBI), however the exact inflammatory mechanisms remain unknown. This study investigated the role of bradykinin and its receptor, which are known initial mediators within inflammation activation, as well as the mechanisms of the cytosolic phospholipase A2 (cPLA2 )-related inflammatory responses after TBI. We found that cPLA2 and bradykinin B2 receptor were upregulated after a TBI. Rats treated with the bradykinin B2 receptor inhibitor LF 16-0687 exhibited significantly less cPLA2 expression and related inflammatory responses in the brain cortex after sustaining a controlled cortical impact (CCI) injury...
June 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29888272/aminophylline-and-ephedrine-but-not-flumazenil-inhibit-the-activity-of-the-excitatory-amino-acid-transporter-3-expressed-in-xenopus-oocytes-and-reverse-the-increased-activity-by-propofol
#11
Sohyeon Moon, Hee Jung Baik
We investigated the effects of flumazenil, aminophylline, and ephedrine on the excitatory amino acid transporter type 3 (EAAT3) activity and the interaction with propofol. EAAT3 was expressed in the Xenopus oocytes. L-Glutamate-induced membrane currents were measured using the two-electrode voltage clamp at various drug concentrations. Oocytes were preincubated with protein kinase C- (PKC-) activator, or inhibitor, and phosphatidylinositol 3-kinase (PI3K) inhibitor. To study the interaction with propofol, oocytes were exposed to propofol, propofol + aminophylline, or ephedrine...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29887572/-astrocyte-neuron-lactate-shuttle-the-major-effector-of-astrocytic-pacap-signaling-for-cns-functions
#12
Yuki Kambe, Takashi Kurihara, Atsuro Miyata
Transfer of lactate from astrocytes to neurons is activated when synaptic activity is increased, and this mechanism is now known as the astrocyte-neuron lactate shuttle (ANLS), that could account for the coupling between synaptic activity and energy delivery. Many lines of evidence suggested that ANLS contributes to neuronal activation or synaptic plasticity at the cellular level as well as learning/memory and cocaine addiction at the behavioral level. However, the candidate neurotransmitters which evoke ANLS activation are still under discussion...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29881327/silencing-formin-like-2-inhibits-growth-and-metastasis-of-gastric-cancer-cells-through-suppressing-internalization-of-integrins
#13
Banghua Zhong, Kewei Wang, Hao Xu, Fanmin Kong
Background: Formin-like 2 (FMNL2) is a member of Formin family which governs cytokinesis, cellular polarity and morphogenesis. Dysregulation of FMNL2 has been discovered in cancers and is closely related to cancers. However, the role of FMNL2 in gastric cancer remains unclear. In this study, we aimed to investigate the role of FMNL2 in gastric cancer cells. Methods: A FMNL2-specific shRNA was employed to decrease the endogenous expression of FMNL2. Then the degree of proliferation, apoptosis, migration and invasion of gastric cancer cells was assessed by MTT assay, flow cytometry, wound healing assay and transwell assay, respectively...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29880645/choline-transport-links-macrophage-phospholipid-metabolism-and-inflammation
#14
Shayne A Snider, Kaitlyn D Margison, Peyman Ghorbani, Nicholas D LeBlond, Conor O'Dwyer, Julia Rc Nunes, Thao Nguyen, Hongbin Xu, Steffany Al Bennett, Morgan D Fullerton
Choline is an essential nutrient that is required for synthesis of the main eukaryote phospholipid, phosphatidylcholine (PC). Macrophages are innate immune cells that survey and respond to danger and damage signals. Although it is well known that energy metabolism can dictate macrophage function, little is known as to the importance of choline homeostasis in macrophage biology. We hypothesized that the uptake and metabolism of choline is important for macrophage inflammation. Polarization of primary bone marrow macrophages with LPS resulted in an increased rate of choline uptake and higher levels of PC synthesis...
June 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29876879/the-mycobacterial-adjuvant-analogue-tdb-attenuates-neuroinflammation-via-mincle-independent-plc-%C3%AE-1-pkc-erk-signaling-and-microglial-polarization
#15
Mahendravarman Mohanraj, Ponarulselvam Sekar, Horng-Huei Liou, Shwu-Fen Chang, Wan-Wan Lin
Microglial activation has long been recognized as a hallmark of neuroinflammation. Recently, the bacillus Calmette-Guerin (BCG) vaccine has been reported to exert neuroprotective effects against several neurodegenerative disorders. Trehalose-6,6'-dibehenate (TDB) is a synthetic analogue of trehalose-6,6'-dimycolate (TDM, also known as the mycobacterial cord factor) and is a new adjuvant of tuberculosis subunit vaccine currently in clinical trials. Both TDM and TDB can activate macrophages and dendritic cells through binding to C-type lectin receptor Mincle; however, its action mechanism in microglia and their relationship with neuroinflammation are still unknown...
June 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29875655/integrative-analysis-of-hippocampus-gene-expression-profiles-identifies-network-alterations-in-aging-and-alzheimer-s-disease
#16
Vinay Lanke, S T R Moolamalla, Dipanjan Roy, P K Vinod
Alzheimer's disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between aging and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of aging and AD, and their relationship using the hippocampal gene expression profiles of young (20-50 years), aging (70-99 years), and AD (70-99 years)...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29870545/the-pkc-%C3%AE-selective-inhibitor-enzastaurin-impairs-memory-in-middle-aged-rats
#17
Mari N Willeman, Sarah E Mennenga, Ashley L Siniard, Jason J Corneveaux, Matt De Both, Lauren T Hewitt, Candy W S Tsang, Jason Caselli, B Blair Braden, Heather A Bimonte-Nelson, Matthew J Huentelman
Enzastaurin is a Protein Kinase C-β selective inhibitor that was developed to treat cancers. Protein Kinase C-β is an important enzyme for a variety of neuronal functions; in particular, previous rodent studies have reported deficits in spatial and fear-conditioned learning and memory with lower levels of Protein Kinase C-β. Due to Enzastaurin's mechanism of action, the present study investigated the consequences of Enzastaurin exposure on learning and memory in 12-month-old Fischer-344 male rats. Rats were treated daily with subcutaneous injections of either vehicle or Enzastaurin, and behaviorally tested using the spatial reference memory Morris Water Maze...
2018: PloS One
https://www.readbyqxmd.com/read/29870540/cigarette-toxin-4-methylnitrosamino-1-3-pyridyl-1-butanone-nnk-induces-experimental-pancreatitis-through-%C3%AE-7-nicotinic-acetylcholine-receptors-nachrs-in-mice
#18
A A Alahmari, B Sreekumar, V Patel, M Ashat, M Alexandre, A K Uduman, E O Akinbiyi, A Ceplenski, C A Shugrue, T R Kolodecik, N Tashkandi, S W Messenger, G E Groblewski, F S Gorelick, E C Thrower
Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR)...
2018: PloS One
https://www.readbyqxmd.com/read/29867346/pka-and-pkc-modulators-affect-ion-channel-function-and-internalization-of-recombinant-alpha1-and-alpha1-beta-glycine-receptors
#19
Ulrike Breitinger, Lamiaa M Bahnassawy, Dieter Janzen, Vera Roemer, Cord-Michael Becker, Carmen Villmann, Hans-Georg Breitinger
Glycine receptors (GlyRs) are important mediators of fast inhibitory neurotransmission in the mammalian central nervous system. Their function is controlled by multiple cellular mechanisms, including intracellular regulatory processes. Modulation of GlyR function by protein kinases has been reported for many cell types, involving different techniques, and often yielding contradictory results. Here, we studied the effects of protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA) on glycine induced currents in HEK293 cells expressing human homomeric α1 and heteromeric α1-β GlyRs using whole-cell patch clamp techniques as well as internalization assays...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29867151/protein-kinase-c%C3%AE%C2%B5-regulates-nuclear-translocation-of-extracellular-signal-regulated-kinase-which-contributes-to-bradykinin-induced-cyclooxygenase-2-expression
#20
Rei Nakano, Taku Kitanaka, Shinichi Namba, Nanako Kitanaka, Hiroshi Sugiya
The proinflammatory mediator bradykinin stimulated cyclooxygenase-2 (COX-2) expression and subsequently prostaglandin E2 synthesis in dermal fibroblasts. The involvement of B2 receptors and Gαq in the role of bradykinin was suggested by using pharmacological inhibitors. The PKC activator PMA stimulated COX-2 mRNA expression. Bradykinin failed to induce COX-2 mRNA expression in the presence of PKC inhibitors, whereas the effect of bradykinin was observed in the absence of extracellular Ca2+ . Bradykinin-induced COX-2 mRNA expression was inhibited in cells transfected with PKCε siRNA...
June 4, 2018: Scientific Reports
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