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Phospho-AKT

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https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#1
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28800461/design-synthesis-and-biological-evaluation-of-novel-3-substituted-imidazo-1-2-a-pyridine-and-quinazolin-4-3h-one-derivatives-as-pi3k%C3%AE-inhibitors
#2
Yan-Hua Fan, Wei Li, Dan-Dan Liu, Meng-Xuan Bai, Hong-Rui Song, Yong-Nan Xu, SangKook Lee, Zhi-Peng Zhou, Jian Wang, Huai-Wei Ding
Phosphatidylinositol 3-kinase (PI3K) is a pivotal regulator of intracellular signaling pathways and considered as a promising target in the development of a therapeutic treatment of cancer. Among the different PI3K subtypes, the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in majority of human cancers. Therefore, the inhibition of PI3Kα has been considered to be an efficient approach for the treatment of cancer. In this study, two series compounds containing hydrophilic group in imidazo[1,2-a]pyridine and quinazolin-4(3H)-one were synthesized and their antiproliferative activities against five cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638 and A549, were evaluated...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28795272/pet-imaging-on-dynamic-metabolic-changes-after-combination-therapy-of-paclitaxel-and-the-traditional-chinese-medicine-in-breast-cancer-bearing-mice
#3
Yao Chen, Ling Wang, Hao Liu, Fahuan Song, Caiyun Xu, Kai Zhang, Qing Chen, Shuang Wu, Yunqi Zhu, Ying Dong, Min Zhou, Hong Zhang, Mei Tian
PURPOSE: The aim of the study was to non-invasively evaluate the anticancer activity of a traditional Chinese medicine-Huaier, combined with paclitaxel (PTX) in breast cancer bearing mice by detecting dynamic metabolic changes with positron emission tomography (PET). PROCEDURES: Balb/c nude mice were randomly divided into one of the four groups: Huaier, PTX, PTX + Huaier, or the control. PET imaging with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) was performed to monitor the metabolic changes in BT474 (luminal B) and MDA-MB-231 (triple-negative) breast cancer xenografts...
August 9, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28775169/loss-of-igf2-gene-imprinting-in-murine-prostate-promotes-widespread-neoplastic-growth
#4
Nathan Damaschke, Bing Yang, Sachin Bhusari, Mele Avilla, Weixiong Zhong, Michael L Blute, Wei Huang, David F Jarrard
Loss of imprinting (LOI) is an epigenetic event which relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28774332/baicalin-attenuates-chronic-hypoxia-induced-pulmonary-hypertension-via-adenosine-a2a-receptor-induced-sdf-1-cxcr4-pi3k-akt-signaling
#5
Xiaoying Huang, Peiliang Wu, Feifei Huang, Min Xu, Mayun Chen, Kate Huang, Guo-Ping Li, Manhuan Xu, Dan Yao, Liangxing Wang
BACKGROUND: Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo...
August 3, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28769006/mechanistic-study-of-inhibitory-effects-of-metformin-and-atorvastatin-in-combination-on-prostate-cancer-cells-in-vitro-and-in-vivo
#6
Zhen-Shi Wang, Hua-Rong Huang, Lan-Yue Zhang, Seungkee Kim, Yan He, Dong-Li Li, Chelsea Farischon, Kun Zhang, Xi Zheng, Zhi-Yun Du, Susan Goodin
Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28759294/epidermal-growth-factor-receptor-activation-promotes-ada3-acetylation-through-the-akt-p300-pathway
#7
Shashank Srivastava, Shakur Mohibi, Sameer Mirza, Hamid Band, Vimla Band
The ADA3 (Alteration/Deficiency in Activation 3) protein is an essential adaptor component of several Lysine Acetyltransferase (KAT) complexes involved in chromatin modifications. Previously, we and others have demonstrated a crucial role of ADA3 in cell cycle progression and maintenance of genomic stability. Recently, we have shown that acetylation of ADA3 is key to its role in cell cycle progression. Here, we demonstrate that AKT activation downstream of Epidermal Growth Factor Receptor (EGFR) family proteins stimulation leads to phosphorylation of p300, which in turn promotes the acetylation of ADA3...
July 31, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28748356/pd-l1-induced-by-ifn-%C3%AE-from-tumor-associated-macrophages-via-the-jak-stat3-and-pi3k-akt-signaling-pathways-promoted-progression-of-lung-cancer
#8
Xiaohui Zhang, Yuanyuan Zeng, Qiuxia Qu, Jianjie Zhu, Zeyi Liu, Weiwei Ning, Hui Zeng, Nan Zhang, Wenwen Du, Cheng Chen, Jian-An Huang
BACKGROUND: Interferon-γ (IFN-γ) is conventionally regarded as an inflammatory cytokine that has a pivotal role in anti-infection and tumor immune surveillance. It has been used clinically to treat a variety of malignancies. However, increased evidence has suggested IFN-γ can act to induce tumor progression. The role of IFN-γ in regulating antitumor immunity appears to be complex and paradoxical. The mechanism underlying the dual aspects of IFN-γ function in antitumor immunity is not clear...
July 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28739689/lxr-activation-down-regulates-lipid-raft-markers-flot2-and-dhhc5-in-mcf-7-breast-cancer-cells
#9
Delphine Carbonnelle, Trang H Luu, Chloe Chaillou, Jean-Michel Huvelin, Jean-Marie Bard, Hassan Nazih
BACKGROUND/AIM: Lipid rafts are cholesterol-enriched microdomains of the plasma membrane. Recent studies have underlined that their integrity is critical for cancer cell survival. Liver X receptor (LXR) has a central role in cellular cholesterol homeostasis and its stimulation inhibits proliferation of several cancer cell lines. This study investigated whether LXR could modulate lipid rafts integrity and consequently alter proliferation of the MCF-7 breast cancer cell line. MATERIALS AND METHODS: Effect of LXR agonist T0901317 on integrity of MCF-7 lipid rafts was examined by studying the expression of rafts marker flotillin-2 (FLOT2) and DHHC5, which palmitoylates FLOT2, and by studying the expression of phospho-Akt...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28699905/fkbp51-decreases-cell-proliferation-and-increases-progestin-sensitivity-of-human-endometrial-adenocarcinomas-by-inhibiting-akt
#10
Jing Dong, Yulian Jiao, Wenli Mu, Bingru Lu, Muyun Wei, Linying Sun, Shengnan Hu, Bin Cui, Xiaowen Liu, Zijiang Chen, Yueran Zhao
In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685413/telluric-acid-ameliorates-endotoxemic-kidney-injury-in-mice-involvement-of-tlr4-nrf2-and-pi3k-akt-signaling-pathways
#11
Ahmed F Mohamed, Marwa M Safar, Hala F Zaki, Helmy M Sayed
Being one of the most abundant trace elements in the human body, the therapeutic potential of tellurium-based compounds has been a target of interest. Recent reports denoted their redox-modulating and anti-inflammatory activities in experimental endotoxemia. However, their potential nephroprotective effect against endotoxemic kidney injury is yet to be elucidated. This study investigated the possible renoprotective effect of telluric acid (TEL) against lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, targeting toll-like receptor 4 (TLR4), phosphoinositide 3-kinase (PI3K)/Akt, and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways as possible mechanistic contributors to TEL's effect...
July 6, 2017: Inflammation
https://www.readbyqxmd.com/read/28679060/protective-effects-of-green-tea-polyphenol-epigallocatechin-3-gallate-against-sevoflurane-induced-neuronal-apoptosis-involves-regulation-of-creb-bdnf-trk-b-and-pi3k-akt-mtor-signalling-pathways-in-neonatal-mice
#12
Mei-Li Ding, Hui Ma, Yi-Gang Man, Yan-Hong Lv
Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea is an effective antioxidant and possesses neuroprotective effects. For neurogenesis and synaptic plasticity, brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucially involved. In this study we aimed to assess protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50 or 75 mg/kg b.wt) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3 %; 6 h) exposure on P7...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28676338/dyrk2-involved-in-regulating-lps-induced-neuronal-apoptosis
#13
Yuxiang Sun, Xin Ge, Mengmeng Li, Li Xu, Yaodong Shen
The activation of relevant signaling pathways plays a very important role in LPS-induced neuronal damage. Dual-specificity tyrosine-phosphorylation-regulated kinase 2(Dyrk2), as a phosphokinase that can directly or indirectly phosphorylate signal molecules, was recently reported to down-regulate Type I Interferon(TIF) by promoting ser527 phosphorylation of TBK1. To further investigate the role of Dyrk2 in neuroinflammation, we for the first time focused on its function in LPS-induced neuronal damage. We found LPS stimulation increased the expression of Dyrk2 in the nucleus and cytoplasm of neurons...
July 1, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28658664/differential-gene-and-lncrna-expression-in-the-lower-thoracic-spinal-cord-following-ischemia-reperfusion-induced-acute-kidney-injury-in-rats
#14
Qing-Quan Liu, Hui Liu, Zhi-Gang He, Shi-Jie Zhang, Bao-Wen Liu, Le Wang, Wen-Hui Qiu, Qing Xu, Hong-Bing Xiang, Yong-Man Lv
We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631564/indole-3-carbinol-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-through-suppression-of-stat5-and-akt-signaling-pathways
#15
Majid Safa, Leila Jafari, Fatemeh Alikarami, Rima Manafi Shabestari, Ahmad Kazemi
Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, idenication of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627671/downregulation-of-notch1-inhibits-the-invasion-and-metastasis-of-human-gastric-cancer-cells-sgc7901-and-mkn74-in%C3%A2-vitro-through-pten-activation-and-dephosphorylation-of-akt-and-fak
#16
Xue-Song Zhang, Yan-Hua Hu, Hong-Yu Gao, Xiu-Wen Lan, Ying-Wei Xue
Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28620824/l-3-n-butylphthalide-activates-akt-mtor-signaling-inhibits-neuronal-apoptosis-and-autophagy-and-improves-cognitive-impairment-in-mice-with-repeated-cerebral-ischemia-reperfusion-injury
#17
Jing Xu, Yaping Huai, Nan Meng, Yanhong Dong, Zhijuan Liu, Qianqian Qi, Ming Hu, Mingyue Fan, Wei Jin, Peiyuan Lv
L-3-n-Butylphthalide (L-NBP) exerts neuroprotective effects in animal models of cerebral ischemia, but its potential benefits in repeated cerebral ischemia-reperfusion (RCIR) injury remain unknown. We investigated the effect of L-NBP on cognitive impairment induced by RCIR in mice. Male C57Bl/6 mice received sham surgery or bilateral common carotid artery occlusion (3 times, 20 min each) and were orally administered preoperative L-NBP (30 mg/kg/day, 7 days), postoperative L-NBP (30 or 60 mg/kg/day, 28 days) or postoperative vehicle (28 days)...
June 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28616662/perifosine-enhances-bevacizumab-induced-apoptosis-and-therapeutic-efficacy-by-targeting-pi3k-akt-pathway-in-a-glioblastoma-heterotopic-model
#18
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mohammad Taghi Joghataei
Bevacizumab (BVZ) as an antiangiogenesis therapy leads to a transient therapeutic efficacy in high-grade glioma. However, the proapoptotic potential of BVZ has not been well elucidated, yet. There is also a tumor resistance to BVZ that is linked to post-treatment metalloproteinases and AKT activities. Herein, the association between therapeutic efficacy and putative proapoptotic activity of low-dose BVZ either alone or in combination with a specific inhibitor of AKT called perifosine (PRF), in a glioma model was investigated...
June 14, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#19
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28562590/genetic-wiring-maps-of-single-cell-protein-states-reveal-an-off-switch-for-gpcr-signalling
#20
Markus Brockmann, Vincent A Blomen, Joppe Nieuwenhuis, Elmer Stickel, Matthijs Raaben, Onno B Bleijerveld, A F Maarten Altelaar, Lucas T Jae, Thijn R Brummelkamp
As key executers of biological functions, the activity and abundance of proteins are subjected to extensive regulation. Deciphering the genetic architecture underlying this regulation is critical for understanding cellular signalling events and responses to environmental cues. Using random mutagenesis in haploid human cells, we apply a sensitive approach to directly couple genomic mutations to protein measurements in individual cells. Here we use this to examine a suite of cellular processes, such as transcriptional induction, regulation of protein abundance and splicing, signalling cascades (mitogen-activated protein kinase (MAPK), G-protein-coupled receptor (GPCR), protein kinase B (AKT), interferon, and Wingless and Int-related protein (WNT) pathways) and epigenetic modifications (histone crotonylation and methylation)...
June 8, 2017: Nature
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