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https://www.readbyqxmd.com/read/28237722/dapper1-attenuates-hepatic-gluconeogenesis-and-lipogenesis-by-activating-pi3k-akt-signaling
#1
Jian-Ren Kuang, Zhi-Hui Zhang, Wei-Ling Leng, Xiao-Tian Lei, Zi-Wen Liang
Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca(2+)-mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver...
February 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28236618/common-1h-mrs-characteristics-in-patients-with-alzheimer-s-disease-and-vascular-dementia-diagnosed-with-kidney-essence-deficiency-syndrome-a-preliminary-study
#2
Zhongwei Guo, Xiaozheng Liu, Yulin Cao, Hongtao Hou, Xingli Chen, Yongcan Chen, Feihua Huang, Wei Chen
Context • Traditional Chinese medicine (TCM) indicates that both Alzheimer's disease (AD) and vascular dementia (VD) should be categorized as dementia and that they have a common etiology and pathogenesis under TCM classification of syndromes, such as with kidney essence deficiency syndrome (KEDS). The pathological location is mainly in the brain. However, it remains unclear whether AD and VD patients with KEDS exhibit a metabolic commonality in the same region of the brain. Objective • The study intended to investigate the metabolic characteristics of the brain using proton magnetic resonance spectroscopy (1H-MRS) in patients with AD and VD who had been diagnosed with KEDS...
February 27, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28235389/structure-based-modelling-scoring-screening-and-in-vitro-kinase-assay-of-anesthetic-pkc-inhibitors-against-a-natural-medicine-library
#3
B X Shi, F R Chen, X Sun
Protein kinase C (PKC) is an intracellular effector of the inositol phosphate-mediated signal transduction pathway. Evidence is emerging that certain general anaesthetics can influence the activity of PKC by interacting with the regulatory domain of the enzyme, and targeting PKC kinase domain is considered as a strategy to modulate the anaesthetic effects. Here, an integrated method was used to perform virtual screening against a large library of natural compounds for the discovery of new and potent PKC modulators...
February 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28229251/taurine-ameliorated-homocysteine-induced-h9c2-cardiomyocyte-apoptosis-by-modulating-endoplasmic-reticulum-stress
#4
Zhimin Zhang, Lianyou Zhao, Yanfen Zhou, Xuanhao Lu, Zhengqiang Wang, Jipeng Wang, Wei Li
Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms...
February 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28223451/mycobacterium-tuberculosis-proteasome-accessory-factor-a-pafa-can-transfer-prokaryotic-ubiquitin-like-protein-pup-between-substrates
#5
Susan Zhang, Kristin E Burns-Huang, Guido V Janssen, Huilin Li, Huib Ovaa, Lizbeth Hedstrom, K Heran Darwin
The protein degradation machinery of Mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. Free Pup is unstable and never observed in extracts of M. tuberculosis, an observation that led us to hypothesize that PafA may need alternative sources of Pup. Here, we show that PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log)...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#6
Clémence Thomas, Whitney Henry, Benjamin G Cuiffo, Anthony Y Collmann, Elisabetta Marangoni, Vanessa Benhamo, Manoj K Bhasin, Cheng Fan, Laetitia Fuhrmann, Albert S Baldwin, Charles Perou, Anne Vincent-Salomon, Alex Toker, Antoine E Karnoub
Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28222026/hypoxic-regulation-of-the-expression-of-genes-encoded-estrogen-related-proteins-in-u87-glioma-cells-eff-ect-of-ire1-inhibition
#7
Minchenko Do, Riabovol Oo, Ratushna Oo, Minchenko Oh
OBJECTIVE: The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation...
January 1, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28220501/chronic-alcohol-feeding-potentiates-hormone-induced-calcium-signalling-in-hepatocytes
#8
Paula J Bartlett, Anil Noronha Antony, Amit Agarwal, Mauricette Hilly, Victoria L Prince, Laurent Combettes, Jan B Hoek, Lawrence D Gaspers
"Adaptive" responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca(2+) ]i ) increases, which can adversely affect mitochondrial Ca(2+) levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca(2+) -mobilizing hormones resulting in more sustained and prolonged [Ca(2+) ]i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver...
February 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28216651/deficiency-of-the-g-protein-g%C3%AE-q-ameliorates-experimental-autoimmune-encephalomyelitis-with-impaired-dc-derived-il-6-production-and-th17-differentiation
#9
Weiming Lai, Yingying Cai, Jinfeng Zhou, Shuai Chen, Chaoyan Qin, Cuixia Yang, Junling Liu, Xin Xie, Changsheng Du
Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and ~40% of all identified GPCRs rely on the Gαq/11 G protein family to stimulate inositol lipid signaling. However, the function of Gα subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gαq in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, Gαq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination...
February 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28214885/signaling-pathway-for-endothelin-1-and-phenylephrine-induced-camp-response-element-binding-protein-activation-in-rat-ventricular-myocytes-role-of-inositol-1-4-5-trisphosphate-receptors-and-camkii
#10
Krishna P Subedi, Min-Jeong Son, Bojjibabu Chidipi, Seong-Woo Kim, Jun Wang, Kyeong-Hee Kim, Joon-Chul Kim, Sun-Hee Woo
BACKGROUND/AIMS: Endothelin-1 (ET-1) and the α1-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. METHODS: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes...
26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#11
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212289/the-effects-of-myo-inositol-and-b-and-d-vitamin-supplementation-in-the-db-mouse-model-of-gestational-diabetes-mellitus
#12
Jasmine F Plows, Florence Budin, Rebecka A M Andersson, Valerie J Mills, Katherine Mace, Sandra T Davidge, Mark H Vickers, Philip N Baker, Irma Silva-Zolezzi, Joanna L Stanley
Gestational diabetes mellitus (GDM) is a growing concern, affecting an increasing number of pregnant women worldwide. By predisposing both the affected mothers and children to future disease, GDM contributes to an intergenerational cycle of obesity and diabetes. In order to stop this cycle, safe and effective treatments for GDM are required. This study sought to determine the treatment effects of dietary supplementation with myo-inositol (MI) and vitamins B2, B6, B12, and D in a mouse model of GDM (pregnant db/+ dams)...
February 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28211945/ip3-receptor-mutations-and-brain-diseases-in-human-and-rodents
#13
REVIEW
Chihiro Hisatsune, Katsuhiko Mikoshiba
The inositol 1,4,5 trisphosphate receptor (IP3 R) is a huge Ca(2+) channel that is localized at the endoplasmic reticulum (ER). The IP3 R releases Ca(2+) from the ER upon binding to IP3 , which is produced by various extracellular stimuli through phospholipase C activation. All vertebrate organisms have three subtypes of IP3 R genes, which have distinct properties of IP3 -binding and Ca(2+) sensitivity, and are differently regulated by phosphorylation and by their associated proteins. Each cell type expresses the three subtypes of IP3 R in a distinct proportion, which is important for creating and maintaining spatially and temporally appropriate intracellular Ca(2+) level patterns for the regulation of specific physiological phenomena...
February 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28208829/calcium-signaling-in-interstitial-cells-focus-on-telocytes
#14
REVIEW
Beatrice Mihaela Radu, Adela Banciu, Daniel Dumitru Banciu, Mihai Radu, Dragos Cretoiu, Sanda Maria Cretoiu
In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca(2+) oscillations, the inositol triphosphate (IP₃)/Ca(2+) signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#15
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28203518/inositol-1-4-5-trisphosphate-receptor-determines-intracellular-ca-2-concentration-in-trypanosoma-cruzi-throughout-its-life-cycle
#16
Muneaki Hashimoto, Motomichi Doi, Nagomi Kurebayashi, Koji Furukawa, Hiroko Hirawake-Mogi, Yoshihiro Ohmiya, Takashi Sakurai, Toshihiro Mita, Katsuhiko Mikoshiba, Takeshi Nara
Regulation of intracellular Ca(2+) concentration ([Ca(2+)]i) is vital for eukaryotic organisms. Recently, we identified a Ca(2+) channel (TcIP 3R) associated with intracellular Ca(2+) stores in Trypanosoma cruzi, the parasitic protist that causes Chagas disease. In this study, we measured [Ca(2+)]i during the parasite life cycle and determined whether TcIP 3R is involved in the observed variations. Parasites expressing R-GECO1, a red fluorescent, genetically encoded Ca(2+) indicator for optical imaging that fluoresces when bound to Ca(2+), were produced...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28203104/proton-magnetic-resonance-spectroscopy-assessment-of-metabolite-status-of-the-anterior-cingulate-cortex-in-chronic-pain-patients-and-healthy-controls
#17
Takahiro Ito, Sachiko Tanaka-Mizuno, Narihito Iwashita, Ikuo Tooyama, Akihiko Shiino, Katsuyuki Miura, Sei Fukui
BACKGROUND: Chronic pain is a common cause of reduced quality of life. Recent studies suggest that chronic pain patients have a different brain neurometabolic status to healthy people. Proton magnetic resonance spectroscopy ((1)H-MRS) can determine the concentrations of metabolites in a specific region of the brain without being invasive. PATIENTS AND METHODS: We recruited 56 chronic pain patients and 60 healthy controls to compare brain metabolic characteristics...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#18
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28202503/vitamin-d-and-depression-cellular-and-regulatory-mechanisms
#19
REVIEW
Michael J Berridge
Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca(2+) within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca(2+) from the internal stores...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28202308/nanaomycin-h-a-new-nanaomycin-analog
#20
Takuji Nakashima, Toru Kimura, Rei Miyano, Hirotaka Matsuo, Tomoyasu Hirose, Aoi Kimishima, Kenichi Nonaka, Masato Iwatsuki, Jun Nakanishi, Yōko Takahashi, Satoshi Ōmura
Physicochemical screening identified a new nanaomycin analog, nanaomycin H, which was isolated from a culture broth of Streptomyces rosa subsp. notoensis OS-3966. This microorganism is already known to produce seven nanaomycin compounds, (nanaomycin A to G). Structural elucidation of nanaomycin H showed it to be a pyranonaphthoquinone with a mycothiol moiety. A N-acetylcysteine S-conjugate of nanaomycin H, without α-glucosamine linked to myo-inositol moiety, mercapturic acid derivative, was also detected in the same culture broth...
February 12, 2017: Journal of Bioscience and Bioengineering
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