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https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#1
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#2
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28428626/c1qbp-suppresses-cell-adhesion-and-metastasis-of-renal-carcinoma-cells
#3
Yong Wang, Donghe Fu, Jing Su, Yajing Chen, Can Qi, Yin Sun, Yuanjie Niu, Ning Zhang, Dan Yue
Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424497/the-glycogen-synthase-kinase-mogsk1-regulated-by-mps1-map-kinase-is-required-for-fungal-development-and-pathogenicity-in-magnaporthe-oryzae
#4
Tengsheng Zhou, Yasin F Dagdas, Xiaohan Zhu, Shiqin Zheng, Liqiong Chen, Zachary Cartwright, Nicholas J Talbot, Zonghua Wang
Magnaporthe oryzae, the causal agent of blast disease, is one of the most destructive plant pathogens, causing significant yield losses on staple crops such as rice and wheat. The fungus infects plants with a specialized cell called an appressorium, whose development is tightly regulated by MAPK signaling pathways following the activation of upstream sensors in response to environmental stimuli. Here, we show the expression of the Glycogen synthase kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly under the stressed conditions...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423622/hnrnpk-mir-223-fbxw7-feedback-cascade-promotes-pancreatic-cancer-cell-growth-and-invasion
#5
D He, Cheng Huang, Qingxin Zhou, Dawei Liu, Longhui Xiong, Hongxia Xiang, Guangnian Ma, Zhiyong Zhang
Several studies have identified miR-223 critically involved in various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action and regulatory mechanisms in PDAC remains largely unclear. In this study, we found that the expression levels of miR-223 were increased in clinical samples with PDAC (81.6%). The upregulation of miR-223 increases the proliferation, migration, and invasive abilities of PDAC cells in vitro and in vivo. Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7 reverted miR-223- induced drastic proliferation in PDAC cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423582/parthenolide-suppresses-non-small-cell-lung-cancer-glc-82-cells-growth-via-b-raf-mapk-erk-pathway
#6
Minting Lin, Hong Bi, Yanyan Yan, Wenjing Huang, Guiping Zhang, Genshui Zhang, Sili Tang, Yun Liu, Lingling Zhang, Jinxiang Ma, Jianye Zhang
Non-small cell lung cancer (NSCLC), one type of lung cancer, owns high rates of morbidity and mortality. B-Raf is one of the promising oncogenic drivers of NSCLC. Parthenolide, a natural product, is mainly extracted from the herbal plant Tanacetum parthenium. The effect of parthenolide on NSCLC cells and its potential as B-Raf inhibitor were studied in this study. It's shown that parthenolide exhibited the strong cytotoxicity against NSCLC cells with IC50 ranging from 6.07 ± 0.45 to 15.38 ± 1.13 μM. Parthenolide was also able to induce apoptosis, suppress proliferation and invasion in NSCLC cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421542/neural-stem-cell-transplantation-promotes-functional-recovery-from-traumatic-brain-injury-via-brain-derived-neurotrophic-factor-mediated-neuroplasticity
#7
Liu-Lin Xiong, Yue Hu, Piao Zhang, Zhuo Zhang, Li-Hong Li, Guo-Dong Gao, Xin-Fu Zhou, Ting-Hua Wang
Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10(5)/μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28418862/niclosamide-is-a-potential-therapeutic-for-familial-adenomatosis-polyposis-by-disrupting-axin-gsk3-interaction
#8
Sung Yong Ahn, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Ji Hye Yang, So Young Cha, Eunae Sandra Cho, Yoonmi Lee, Jeong Seok Cha, Hyun Soo Cho, Yoon Jeon, Young-Su Yuk, Suebean Cho, Kyoung Tai No, Hyun Sil Kim, Ho Lee, Jiwon Choi, Jong In Yook
The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414160/paraquat-induces-extrinsic-pathway-of-apoptosis-in-a549-cells-by-induction-of-dr5-and-repression-of-anti-apoptotic-proteins-ddx3-and-gsk3-expression
#9
Sasiphen Hathaichoti, Daranee Visitnonthachai, Pronrumpa Ngamsiri, Apichaya Niyomchan, Oyu Tsogtbayar, Churaibhon Wisessaowapak, Piyajit Watcharasit, Jutamaad Satayavivad
Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity partly through induction of apoptosis. Here we demonstrated that PQ caused apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating caspase-8 activation and truncated Bid, the two key mediators of extrinsic apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor-5) and caspase-8 interaction, indicating formation of DISC (death-inducing signaling complex). These results indicate that PQ induces apoptosis through extrinsic pathway in A549 cells...
April 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28408662/the-gdnf-responsive-phosphoprotein-landscape-identifies-raptor-phosphorylation-required-for-spermatogonial-progenitor-cell-proliferation
#10
Min Wang, Yueshuai Guo, Mei Wang, Tao Zhou, Yuanyuan Xue, Guihua Du, Xiang Wei, Jing Wang, Lin Qi, Hao Zhang, Lufan Li, Lan Ye, Xuejiang Guo, Xin Wu
Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including stem cells support life-long spermatogenesis and male fertility, but pivotal phosphorylation events that regulate fate decisions in SPCs remain unresolved. Here, we described a quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of SPCs following sustained stimulation with glial cell-derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC proliferation...
April 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28399398/selective-autophagy-of-bes1-mediated-by-dsk2-balances-plant-growth-and-survival
#11
Trevor M Nolan, Benjamin Brennan, Mengran Yang, Jiani Chen, Mingcai Zhang, Zhaohu Li, Xuelu Wang, Diane C Bassham, Justin Walley, Yanhai Yin
Plants encounter a variety of stresses and must fine-tune their growth and stress-response programs to best suit their environment. BES1 functions as a master regulator in the brassinosteroid (BR) pathway that promotes plant growth. Here, we show that BES1 interacts with the ubiquitin receptor protein DSK2 and is targeted to the autophagy pathway during stress via the interaction of DSK2 with ATG8, a ubiquitin-like protein directing autophagosome formation and cargo recruitment. Additionally, DSK2 is phosphorylated by the GSK3-like kinase BIN2, a negative regulator in the BR pathway...
April 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28397338/glycogen-synthase-kinase-3-inhibitors-suppress-the-ar-v7-mediated-transcription-and-selectively-inhibit-cell-growth-in-ar-v7-positive-prostate-cancer-cells
#12
Daisuke Nakata, Ryokichi Koyama, Kazuhide Nakayama, Satoshi Kitazawa, Tatsuya Watanabe, Takahito Hara
BACKGROUND: Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. METHODS: High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system...
April 10, 2017: Prostate
https://www.readbyqxmd.com/read/28383811/hsf1-phosphorylation-by-erk-gsk3-suppresses-rnf126-to-sustain-igf-iir-expression-for-hypertension-induced-cardiomyocyte-hypertrophy
#13
Chih-Yang Huang, Fa-Lun Lee, Shu-Fen Peng, Kuan-Ho Lin, Ray-Jade Chen, Tsung-Jung Ho, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT1 R)...
April 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28381545/drug-resistance-mechanisms-in-colorectal-cancer-dissected-with-cell-type-specific-dynamic-logic-models
#14
Federica Eduati, Victoria Doldàn-Martelli, Bertram Klinger, Thomas Cokelaer, Anja Sieber, Fiona Kogera, Mathurin Dorel, Mathew J Garnett, Nils Blüthgen, Julio Saez-Rodriguez
Genomic features are used as biomarkers of sensitivity to kinase inhibitors used widely to treat human cancer, but effective patient stratification based on these principles remains limited in impact. Insofar as kinase inhibitors interfere with signaling dynamics, and, in turn, signaling dynamics affects inhibitor responses, we investigated associations in this study between cell-specific dynamic signaling pathways and drug sensitivity. Specifically, we measured 14 phosphoproteins under 43 different perturbed conditions (combinations of 5 stimuli and 7 inhibitors) in 14 colorectal cancer cell lines, building cell line-specific dynamic logic models of underlying signaling networks...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28368397/molecular-impact-of-selective-nfkb1-and-nfkb2-signaling-on-dlbcl-phenotype
#15
X Guo, J L Koff, A B Moffitt, M Cinar, S Ramachandiran, Z Chen, J M Switchenko, M Mosunjac, S G Neill, K P Mann, M Bagirov, Y Du, Y Natkunam, H J Khoury, M R Rossi, W Harris, C R Flowers, I S Lossos, L H Boise, S S Dave, J Kowalski, L Bernal-Mizrachi
Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28363635/glycogen-synthase-kinase-3-gsk3-regulates-tnf-production-and-haemocyte-phagocytosis-in-the-immune-response-of-chinese-mitten-crab-eriocheir-sinensis
#16
Xiaowei Li, Zhihao Jia, Weilin Wang, Lingling Wang, Zhaoqun Liu, Bin Yang, Yunke Jia, Xiaorui Song, Qilin Yi, Limei Qiu, Linsheng Song
Glycogen synthase kinase-3 (GSK3) is a serine/threonine protein kinase firstly identified as a regulator of glycogen synthesis. Recently, it has been proved to be a key regulator of the immune reaction. In the present study, a GSK3 homolog gene (designated as EsGSK3) was cloned from Chinese mitten crab, Eriocheir sinensis. The open reading frame (ORF) was 1824 bp, which encoded a predicted polypeptide of 607 amino acids. There was a conserved Serine/Threonine Kinase domain and a DNA binding domain found in EsGSK3...
March 29, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28361047/dynamic-akt-mtor-signaling-in-children-with-autism-spectrum-disorder
#17
Charity Onore, Houa Yang, Judy Van de Water, Paul Ashwood
Autism spectrum disorder (ASD) is a behaviorally defined disorder affecting 1 in 68 children. Currently, there is no known cause for the majority of ASD cases nor are there physiological diagnostic tools or biomarkers to aid behavioral diagnosis. Whole-genome linkage studies, genome-wide association studies, copy number variation screening, and SNP analyses have identified several ASD candidate genes, but which vary greatly among individuals and family clusters, suggesting that a variety of genetic mutations may result in a common pathology or alter a common mechanistic pathway...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#18
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#19
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28296942/co-ingestion-of-carbohydrate-and-whey-protein-increases-fasted-rates-of-muscle-protein-synthesis-immediately-after-resistance-exercise-in-rats
#20
Wanyi Wang, Zhenping Ding, Geoffrey J Solares, Soon-Mi Choi, Bo Wang, Aram Yoon, Roger P Farrar, John L Ivy
The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise...
2017: PloS One
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