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https://www.readbyqxmd.com/read/29352519/nafamostat-mesilate-attenuates-inflammation-and-apoptosis-and-promotes-locomotor-recovery-after-spinal-cord-injury
#1
Hui-Quan Duan, Qiu-Li Wu, Xue Yao, Bao-You Fan, Hong-Yu Shi, Chen-Xi Zhao, Yan Zhang, Bo Li, Chao Sun, Xiao-Hong Kong, Xin-Fu Zhou, Shi-Qing Feng
AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352251/differential-effects-of-sumo1-and-sumo3-on-pkr-activation-and-stability
#2
Ghizlane Maarifi, Faten El Asmi, Mohamed Ali Maroui, Laurent Dianoux, Mounira K Chelbi-Alix
Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is a serine/threonine kinase that exerts its own phosphorylation and the phosphorylation of the α subunit of the protein synthesis initiation factor eIF-2α. PKR was identified as a target of SUMOylation and the triple PKR-SUMO deficient mutant on Lysine residues K60-K150-K440 has reduced PKR activity. We report that SUMO1 and SUMO3 expression exert differential effects on PKR localization, activation and stability. SUMO1 or SUMO3 did not alter the repartition of PKR in the cytoplasm and the nucleus...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352143/ribosomal-protein-us7-rps5-serine-223-in-protein-kinase-mediated-phosphorylation-and-ribosomal-small-subunit-maturation
#3
Makoto Tomioka, Mitsugu Shimobayashi, Makoto Kitabatake, Mutsuhito Ohno, Yasunori Kozutsumi, Shogo Oka, Hiromu Takematsu
Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352075/o-linked-%C3%AE-n-acetylglucosamine-o-glcnac-modification-a-new-pathway-to-decode-pathogenesis-of-diabetic-retinopathy
#4
REVIEW
Zafer Gurel, Nader Sheibani
The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29350679/proangiogenic-functions-of-an-rgd-slay-containing-osteopontin-icosamer-peptide-in-huvecs-and-in-the-postischemic-brain
#5
Hahnbie Lee, Yin-Chuan Jin, Seung-Woo Kim, Il-Doo Kim, Hye-Kyung Lee, Ja-Kyeong Lee
Osteopontin (OPN) is a phosphorylated glycoprotein secreted into body fluids by various cell types. OPN contains arginine-glycine-aspartate (RGD) and serine-leucine-alanine-tyrosine (SLAY) motifs that bind to several integrins and mediate a wide range of cellular processes. In the present study, the proangiogenic effects of a 20-amino-acid OPN peptide (OPNpt20) containing RGD and SLAY motifs were examined in human umbilical vein endothelial cells (HUVECs) and in a rat focal cerebral ischemia model. OPNpt20 exerted robust proangiogenic effects in HUVECs by promoting proliferation, migration and tube formation...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29348626/arabidopsis-serine-threonine-tyrosine-protein-kinase-phosphorylates-oil-body-proteins-that-regulate-oil-content-in-the-seeds
#6
Iyappan Ramachandiran, Anitha Vijayakumar, Visvanathan Ramya, Ram Rajasekharan
Protein phosphorylation is an important post-translational modification that can regulate the protein function. The current knowledge on the phosphorylation status of plant oil body (OB) proteins is inadequate. This present study identifies the distinct physiological substrates of Arabidopsis serine/threonine/tyrosine protein kinase (STYK) and its role in seed oil accumulation; the role of Arabidopsis OLE1, a major seed OB protein has also been elucidated. In vitro kinase assay followed by mass spectrometry identifies residue that are phosphorylated by STYK...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348584/quail-egg-homogenate-alleviates-food-allergy-induced-eosinophilic-esophagitis-like-disease-through-modulating-par-2-transduction-pathway-in-peanut-sensitized-mice
#7
Priscilia Lianto, Shiwen Han, Xinrui Li, Fredrick Onyango Ogutu, Yani Zhang, Zhuoyan Fan, Huilian Che
The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#8
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345365/deletion-of-bcg-hip1-protease-enhances-dendritic-cell-and-cd4-t-cell-responses
#9
Erica Bizzell, Jonathan Kevin Sia, Melanie Quezada, Ana Enriquez, Maria Georgieva, Jyothi Rengarajan
Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine strain Mycobacterium bovis Bacille Calmette-Guérin (BCG) shares many of the immune evasion proteins utilized by Mtb, but the role of these proteins in DC and T cell responses elicited by BCG is poorly understood. We previously reported that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during infection...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345360/mtor-a-double-edged-sword-for-diabetes
#10
REVIEW
Yali Tuo, Ming Xiang
Diabetes is both a metabolic and an immune disorder. One intriguing link between the two is the serine-threonine protein kinase mammalian target of rapamycin (mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR is a key regulator of fuel metabolism and function of both pancreatic islet β cells and immune cells. Consequently, it seems that mTOR has both anti- and prodiabetic effects. On the one hand, activation of mTOR in β cells can increase their growth and proliferation, opposing impairments of insulin secretion in diabetes...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345339/the-role-of-cdk5-mediated-drp1-phosphorylation-in-a%C3%AE-1-42-induced-mitochondrial-fission-and-neuronal-apoptosis
#11
Miao-Yu Guo, Lei Shang, Yang-Yang Hu, Li-Ping Jiang, Yu-Ying Wan, Qin-Qin Zhou, Kun Zhang, Hong-Fei Liao, Jing-Lin Yi, Xiao-Jian Han
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345065/fingolimod-targets-cerebral-endothelial-activation-to-block-leukocyte-recruitment-in-the-central-nervous-system
#12
Yawei Zhao, Dongyan Shi, Kelei Cao, Fengjiao Wu, Xingxing Zhu, Shuang Wen, Qiang You, Keqi Zhang, Lixin Liu, Hong Zhou
Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection. We found that FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in the CNS by inhibiting leukocyte recruitment in cerebral microvessels...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344970/carbon-allocation-to-major-metabolites-in-illuminated-leaves-is-not-just-proportional-to-photosynthesis-when-gaseous-conditions-co2-and-o2-vary
#13
Cyril Abadie, Camille Bathellier, Guillaume Tcherkez
In gas-exchange experiments, manipulating CO2 and O2 is commonly used to change the balance between carboxylation and oxygenation. Downstream metabolism (utilization of photosynthetic and photorespiratory products) may also be affected by gaseous conditions but this is not well documented. Here, we took advantage of sunflower as a model species, which accumulates chlorogenate in addition to sugars and amino acids (glutamate, alanine, glycine and serine). We performed isotopic labelling with 13 CO2 under different CO2 /O2 conditions, and determined 13 C contents to compute 13 C-allocation patterns and build-up rates...
January 18, 2018: New Phytologist
https://www.readbyqxmd.com/read/29344832/mitogen-activated-protein-kinase-6-and-map-kinase-phosphatase-1-are-involved-in-the-response-of-arabidopsis-roots-to-l-glutamate
#14
Jesús Salvador López-Bucio, Javier Raya-González, Gustavo Ravelo-Ortega, León Francisco Ruiz-Herrera, Maricela Ramos-Vega, Patricia León, José López-Bucio, Ángel Arturo Guevara-García
The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood...
January 17, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29344374/cardioprotection-by-an-anti-masp-2-antibody-in-a-murine-model-of-myocardial-infarction
#15
James E Clark, Thomas Dudler, Michael S Marber, Wilhelm Schwaeble
Background: Myocardial ischaemia-reperfusion injury is a major cause of mortality and morbidity in the developed world. Many approaches have been investigated to counteract the pathological consequences associated with acute myocardial infarction (AMI) and cardiac remodelling. It is accepted that inflammation, and therefore activation of the complement pathway, is a crucial step in the pathogenesis of this injury, and many attempts have been made to ameliorate the infarction and consequent dysfunction using anticomplement therapy, with mixed success...
2018: Open Heart
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#16
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344198/combination-of-cecropinxj-and-ly294002-induces-synergistic-cytotoxicity-and-apoptosis-in-human-gastric-cancer-cells-via-inhibition-of-the-pi3k-akt-signaling-pathway
#17
Li-Jie Xia, Yan-Ling Wu, Fu-Chun Zhang
The aim of the present study was to investigate the cytotoxic and apoptotic effects of cecropinXJ against human gastric cancer BGC823 cells, either alone, or in combination with a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. Cell viability and the apoptosis rate were measured using flow cytometry with Annexin-V staining. Additionally, the expression levels of several RAC-α serine/threonine kinase (Akt) phosphorylation-associated proteins and apoptosis-regulating proteins were evaluated by western blot analysis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344164/mastl-overexpression-is-associated-with-epithelial-to-mesenchymal-transition-and-predicts-a-poor-clinical-outcome-in-gastric-cancer
#18
Xian-Jun Sun, Yan-Liang Li, Long-Gang Wang, Li-Qing Liu, Heng Ma, Wen-Hong Hou, Jin-Ming Yu
Microtubule-associated serine/threonine kinase like (Mastl) is deregulated in a number of types of human malignancy and may be a kinase target for cancer treatment. The aim of the present study was to determine the Mastl expression in gastric cancer and to clarify its clinical and prognostic significance. Immunohistochemistry was performed on a cohort of 126 postoperative gastric cancer samples to detect the expression of Mastl and two epithelial to mesenchymal transition (EMT) markers, epithelial-cadherin and Vimentin...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344121/a-five-gene-based-risk-score-with-high-prognostic-value-in-colorectal-cancer
#19
Yida Pan, Hongyang Zhang, Mingming Zhang, Jie Zhu, Jianghong Yu, Bangting Wang, Jigang Qiu, Jun Zhang
Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343826/mammalian-sterile-20-kinase-1-and-2-are-important-regulators-of-hematopoietic-stem-cells-in-stress-condition
#20
Da-Hye Lee, Tae-Shin Kim, Dongjun Lee, Dae-Sik Lim
The mammalian Hippo signaling pathway has been implicated in the self-renewal and differentiation of stem and progenitor cells. MST1 and MST2 (MST1/2) are core serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has been extensively investigated for its role in T cell and myeloid cell function. These studies have identified MST1 as a promising therapeutic target in immunological disease. However, the roles of MST1/2 in hematopoietic stem cell (HSC) function in vivo are not fully understood...
January 17, 2018: Scientific Reports
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