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Phospho-AKT

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https://www.readbyqxmd.com/read/28075049/src-homology-2-domain-containing-inositol-5-phosphatase-ameliorates-high-glucose-induced-extracellular-matrix-deposition-via-the-phosphatidylinositol-3-kinase-protein-kinase-b-pathway-in-renal-tubular-epithelial-cells
#1
Fan Li, Lisha Li, Jun Hao, Shuxia Liu, Huijun Duan
A typical hallmark of diabetic kidney disease (DKD) is an excessive deposition of extracellular matrix (ECM) in the glomerulus and renal tubulointerstitium, leading to glomerulosclerosis and tubular interstitial fibrosis. Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Here, we investigated the effect of SHIP on ECM deposition in diabetic mice and high glucose-stimulated human renal tubular epithelial cells (HK2 cells)...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28074064/o-glcnacylation-of-stat5-controls-tyrosine-phosphorylation-and-oncogenic-transcription-in-stat5-dependent-malignancies
#2
P Freund, M A Kerenyi, M Hager, T Wagner, B Wingelhofer, H T T Pham, M Elabd, X Han, P Valent, F Gouilleux, V Sexl, O H Krämer, B Groner, R Moriggl
The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Posttranslational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28073681/association-of-cytoplasmic-cxcr4-with-loss-of-epithelial-marker-and-activation-of-erk1-2-and-akt-signaling-pathways-in-non-small-cell-lung%C3%A2-cancer
#3
Nabil F Saba, Yuxiang Wang, Hongpeng Fu, Lydia Koenig, Fadlo R Khuri, Dong M Shin, Zhuo Georgia Chen
OBJECTIVES: Compelling evidence demonstrates that CXC-chemokine receptor 4 (CXCR4) is involved in tumor invasion, angiogenesis, metastasis, and resistance to chemotherapy in addition to being one of the coreceptors for T-tropic human immunodeficiency virus entry into T cells. However, it remains controversial as to how to identify functionally activated CXCR4 in tumor biopsies, which would assist in determining which patients may benefit from potential CXCR4-targeted therapy. MATERIALS AND METHODS: Immunohistochemistry (IHC) staining on archival tissues of patients with non-small-cell lung cancer (NSCLC) was used to detect a panel of biomarkers, including phospho-ERK1/2, phospho-AKT, and E-cadherin, which are relevant to downstream signaling of CXCR4 and epithelial to mesenchymal transition (EMT)...
December 22, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28061880/phospho-akt-overexpression-is-prognostic-and-can-be-used-to-tailor-the-synergistic-interaction-of-akt-inhibitors-with-gemcitabine-in-pancreatic-cancer
#4
Daniela Massihnia, Amir Avan, Niccola Funel, Mina Maftouh, Anne van Krieken, Carlotta Granchi, Rajiv Raktoe, Ugo Boggi, Babette Aicher, Filippo Minutolo, Antonio Russo, Leticia G Leon, Godefridus J Peters, Elisa Giovannetti
BACKGROUND: There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. METHODS: Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100)...
January 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28056993/effect-of-active-vitamin-d3-on-vegf-induced-adam33-expression-and-proliferation-in-human-airway-smooth-muscle-cells-implications-for-asthma-treatment
#5
Sung-Ho Kim, Qing-Mei Pei, Ping Jiang, Min Yang, Xue-Jiao Qian, Jiang-Bo Liu
BACKGROUND: Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthma. Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may influence asthma pathogenesis. A disintegrin and metalloproteinase (ADAM)33 has been identified as playing a role in the pathophysiology of asthma...
January 5, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28054340/fingolimod-confers-neuroprotection-through-activation-of-rac1-after-experimental-germinal-matrix-hemorrhage-in-rat-pups
#6
William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Julia LeGrand, Abby Jones Weldon, Liang Xu, John H Zhang
Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism of acute fingolimod-induced protection. GMH was induced in P7 rats by infusion of collagenase (0.3 U) into the right ganglionic eminence. Animals euthanized at four weeks post-GMH received low or high dose fingolimod (0...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28042037/lycorine-induces-apoptosis-of-bladder-cancer-t24-cells-by-inhibiting-phospho-akt-and-activating-the-intrinsic-apoptotic-cascade
#7
Chongshan Wang, Qiongren Wang, Xiezhao Li, Zhong Jin, Peng Xu, Naijin Xu, Abai Xu, Yawen Xu, Shaobo Zheng, Junxia Zheng, Chunxiao Liu, Peng Huang
Lycorine, an alkaloid extracted from Amaryllidaceae genera, exhibits antitumor activities against several human solid-tumor and leukemia cells with extensive influence on various cell signaling molecules. However, the effect of lycorine on bladder cancer has not yet been investigated. In this study, we demonstrated that lycorine induced apoptosis in human bladder cancer T24 cells, an effect that is mediated via inhibition of phospho-Akt expression and the consequent activation of caspase-3 and Bax in vitro...
December 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28042024/metformin-ameliorates-high-uric-acid-induced-insulin-resistance-in-skeletal-muscle-cells
#8
Huier Yuan, Yaqiu Hu, Yuzhang Zhu, Yongneng Zhang, Chaohuan Luo, Zhi Li, Tengfei Wen, Wanling Zhuang, Jinfang Zou, Liangli Hong, Xin Zhang, Ichiro Hisatome, Tetsuya Yamamoto, Jidong Cheng
Hyperuricemia occurs together with abnormal glucose metabolism and insulin resistance. Skeletal muscle is an important organ of glucose uptake, disposal, and storage. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance. Our previous study showed that high uric acid (HUA) induced insulin resistance in skeletal muscle tissue. However, the mechanism of metformin ameliorating UA-induced insulin resistance in muscle cells is unknown and we aimed to determine it...
December 29, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28017896/augmented-o-glcnac-signaling-via-glucosamine-attenuates-oxidative-stress-and-apoptosis-following-contrast-induced-acute-kidney-injury-in-rats
#9
Jiachang Hu, Rongyi Chen, Ping Jia, Yi Fang, Tongqiang Liu, Nana Song, Xialian Xu, Jun Ji, Xiaoqiang Ding
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals. Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI. O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear. Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective...
December 23, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28000865/pi3k-inhibitor-ly294002-as-opposed-to-wortmannin-enhances-akt-phosphorylation-in-gemcitabine-resistant-pancreatic-cancer-cells
#10
Yufeng Wang, Yasuhiro Kuramitsu, Byron Baron, Takao Kitagawa, Kazuhiro Tokuda, Junko Akada, Shin-Ichiro Maehara, Yoshihiko Maehara, Kazuyuki Nakamura
LY294002 and wortmannin are chemical compounds that act as potent inhibitors of phosphoinositide 3-kinases (PI3Ks). Both of them are generally used to inhibit cell proliferation as cancer treatment by inhibiting the PI3K/protein kinase B (AKT) signaling pathway. In this study, LY294002 (but not wortmannin) showed an abnormal ability to enhance AKT phosphorylation (at Ser472) specifically in gemcitabine (GEM)-resistant pancreatic cancer (PC) cell lines PK59 and KLM1-R. LY294002 was shown to activate AKT and accumulate phospho-AKT at the intracellular membrane in PK59, which was abolished by treatment with AKTi-1/2 or wortmannin...
December 14, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27998437/-effects-of-tetrahydrobiopterin-on-the-angiogenesis-in-hepatocellular-carcinoma
#11
Y G Dai, P Gan, W M Li, Q Yao, Y Li, B Pei, J Cui
Objective: To investigate the effect and mechanism of tetrahydrobiopterin (BH4) on the angiogenesis in hepatocellular carcinoma (HCC). Methods: BALB/c-nu mice were subcutaneously injected with HepG-2 cells and randomly divided into control and BH4 groups. The BH4 group and control group received 20 mg/kg BH4 or saline by intraperitoneal injection daily for two weeks, respectively. The level of BH4 was measured by high performance liquid chromatography (HPLC), the level of nitric oxide (NO) was measured by Griess test array, the transcriptional level of K-ras was measured by quantitative RT-PCR, and the protein expressions of guanosine triphosphate cyclohydrolase Ⅰ(GTPCH), endothelial nitric oxide synthase (eNOS), phospho-Akt and Akt were determined by Western blot...
November 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27965087/ship-a-novel-factor-to-ameliorate-extracellular-matrix-accumulation-via-suppressing-pi3k-akt-ctgf-signaling-in-diabetic-kidney-disease
#12
Fan Li, Lisha Li, Meijuan Cheng, Xiumin Wang, Jun Hao, Shuxia Liu, Huijun Duan
Tubular interstitial extracellular matrix accumulation, which plays a key role in the pathogenesis and progression of diabetic kidney disease (DKD), is believed to be mediated by activation of PI3K/Akt signal pathway. However, it is still not clear whether SH2 domain-containing inositol 5'-phosphatase (SHIP), known as a negative regulator of PI3K/Akt pathway is also involved in extracellular matrix metabolism of diabetic kidney. In the present study, decreased SHIP and increased phospho-Akt (Ser 473, Thr 308) were found in renal tubular cells of diabetic mice accompanied by overexpression of connective tissue growth factor (CTGF) and extracellular matrix deposition versus normal mice...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27928692/palmitic-acid-triggers-cell-apoptosis-in-rgc-5-retinal-ganglion-cells-through-the-akt-foxo1-signaling-pathway
#13
Panshi Yan, Shu Tang, Haifeng Zhang, Yuanyuan Guo, Zhiwen Zeng, Qiang Wen
Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells (RGCs). Lipotoxicity, involving a series of pathological cellular responses after exposure to elevated levels of fatty acids, leads to oxidative stress and cell death in various cell types. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O1 (PI3K/Akt/FoxO1) pathway is crucial for cell survival and apoptosis. More importantly, FoxO1 gene has been reported to confer relatively higher risks for eye diseases including glaucoma...
December 7, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27919849/intraportal-mesenchymal-stem-cell-transplantation-prevents-acute-liver-failure-through-promoting-cell-proliferation-and-inhibiting-apoptosis
#14
Jian-Feng Sang, Xiao-Lei Shi, Bin Han, Tao Huang, Xu Huang, Hao-Zhen Ren, Yi-Tao Ding
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. METHODS: The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), peripheral intravenous injection (PV group) and intrahepatic injection (IH group)...
December 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27916377/tetrahydrocurcumin-provides-neuroprotection-in-rats-after-traumatic-brain-injury-autophagy-and-the-pi3k-akt-pathways-as-a-potential-mechanism
#15
Yongyue Gao, Jie Li, Lingyun Wu, Chenhui Zhou, Qiang Wang, Xiang Li, Mengliang Zhou, Handong Wang
BACKGROUND: Tetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI. MATERIAL AND METHODS: Behavioral studies were performed by recording and analyzing beam-walking scores...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27897392/toll-like-receptor-4-signalling-mediates-inflammation-in-skeletal-muscle-of-patients-with-chronic-kidney-disease
#16
Daniela Verzola, Alice Bonanni, Antonella Sofia, Fabrizio Montecucco, Elena D'Amato, Valeria Cademartori, Emanuele Luigi Parodi, Francesca Viazzi, Chiara Venturelli, Giuliano Brunori, Giacomo Garibotto
BACKGROUND: Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine...
October 18, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27895771/co-culture-of-hepatoma-cells-with-hepatocytic-precursor-stem-like-cells-inhibits-tumor-cell-growth-and-invasion-by-downregulating-akt-nf-%C3%AE%C2%BAb-expression
#17
Cheng-Jun Sui, Miao Xu, Wei-Qing Li, Jia-Mei Yang, Hong-Zhu Yan, Hui-Min Liu, Chun-Yan Xia, Hong-Yu Yu
Hepatocytic stem cells (HSCs) have inhibitory effects on hepatocarcinoma cells. The present study investigated the effects of HSC activity in hepatocarcinoma cells in vitro. A Transwell co-culture system of hepatocytic precursor (stem-like) WB-F344 cells and hepatoma CBRH-7919 cells was used to assess HSC activity in metastasized hepatoma cells in vitro. Nude mouse xenografts were used to assess HSC activity in vivo. Co-culture of hepatoma CBRH-7919 cells with WB-F344 cells suppressed the growth and colony formation, tumor cell migration and invasion capacity of CBRH-7919 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27879648/the-role-of-deoxycytidine-kinase-dck-in-radiation-induced-cell-death
#18
Rui Zhong, Rui Xin, Zongyan Chen, Nan Liang, Yang Liu, Shumei Ma, Xiaodong Liu
Deoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the anti-tumor activity for many nucleoside analogs. dCK is activated in response to ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74 by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced cell death is less clear. In this study, we genetically modified dCK expression by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation) and S74E (mimics phosphorylation) of dCK...
November 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27875549/the-synthetic-%C3%AE-nitrostyrene-derivative-cyt-rx20-inhibits-esophageal-tumor-growth-and-metastasis-via-pi3k-akt-and-stat3-pathways
#19
Wen-Chin Chiu, Yi-Chen Lee, Yu-Han Su, Yen-Yun Wang, Chun-Hao Tsai, Yi-An Hou, Chie-Hong Wang, Ying-Fong Huang, Chih-Jen Huang, Shah-Hwa Chou, Pei-Wen Hsieh, Shyng-Shiou F Yuan
The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers...
2016: PloS One
https://www.readbyqxmd.com/read/27867349/baclofen-protects-primary-rat-retinal-ganglion-cells-from-chemical-hypoxia-induced-apoptosis-through-the-akt-and-perk-pathways
#20
Pingping Fu, Qiang Wu, Jianyan Hu, Tingting Li, Fengjuan Gao
Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs...
2016: Frontiers in Cellular Neuroscience
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