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https://www.readbyqxmd.com/read/29108284/overexpression-of-mir-26b-decreases-the-cisplatin-resistance-in-laryngeal-cancer-by-targeting-atf2
#1
Linli Tian, Jiarui Zhang, Xiuxia Ren, Xinyu Liu, Wei Gao, Chen Zhang, Yanan Sun, Ming Liu
Cisplatin is a common used chemotherapeutic drug for the treatment of laryngeal cancer. However, drug-resistance is a major obstacle in platinum-based chemotherapy for laryngeal cancer. Recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is responsible for chemoresistance in multiple cancers including laryngeal cancer, but the potential mechanisms are required to be explored. In the present study, we constantly exposed the laryngeal cancer cell line Hep-2 with cisplatin to establish a cisplatin-resistant laryngeal cancer cell model (Hep-2/R)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107187/generation-of-recombinant-affinity-reagents-against-a-two-phosphosite-epitope-of-atf2
#2
Jennifer McGinnis, Brian K Kay
Activating Transcription Factor 2 (ATF2) plays an important role in mammalian cell proliferation, apoptosis and DNA repair. Its activation is dependent on the sequential phosphorylation of residue threonine 71 (T71) followed by threonine 69 (T69) in its transactivation domain. While these modifications can be directed by a variety of kinases, the time to reach full phosphorylation is dependent on which signaling pathway has been activated, which is thought to be important for proper temporal regulation. To explore this phenomenon further, there have been ongoing efforts to generate affinity reagents for monitoring phosphorylation events in cellular assays...
October 26, 2017: New Biotechnology
https://www.readbyqxmd.com/read/29072705/microrna-145-attenuates-tnf-%C3%AE-driven-cartilage-matrix-degradation-in-osteoarthritis-via-direct-suppression-of-mkk4
#3
Guoli Hu, Xiaoying Zhao, Chuandong Wang, Yiyun Geng, Jingyu Zhao, Jiajia Xu, Bin Zuo, Chen Zhao, Chenglong Wang, Xiaoling Zhang
Cartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and tumor necrosis factor (TNF)-α has critical role in this process by driving inflammatory cascades and cartilage degradation. However, the negative regulation of TNF-α-mediated signaling remains undefined. Here we demonstrate the crucial role of miR-145 in the modulation of TNF-α-mediated signaling and cartilage matrix degradation. MicroRNA (miRNA) expression profiles of TNF-α-stimulated chondrocytes showed that miR-145 expression was rapidly downregulated by TNF-α...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29017144/anxiolytic-effect-of-fatty-acids-and-terpenes-fraction-from-aloysia-triphylla-serotoninergic-gabaergic-and-glutamatergic-implications
#4
Enrique Jiménez-Ferrer, Mayra Alejandra Santillán-Urquiza, Elian Alegría-Herrera, Alejandro Zamilpa, Carmen Noguerón-Merino, Jaime Tortoriello, Victor Navarro-García, Margarita Avilés-Flores, Macrina Fuentes-Mata, Maribel Herrera-Ruiz
Aloysia triphylla (Verbenaceae) is an aromatic medicinal plant, and it is used for the treatment of "nervous" problems as, "sadness" and "nervousness". While, there are no reports about its pharmacological activity in animal models. The objective of this work was to evaluate the anxiolytic effect of the extracts and fractions of this species and to measure the interaction of the most active fraction with serotonergic, glutamatergic and GABAergic drugs. An elevated plus maze test was carried ought where the methanol (AtM), dicloromethane (AtD) and hexanic (AtH) extracts presented anxiolytic activity in mice when exposed to the test...
October 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28982580/stimulation-of-transient-receptor-potential-m3-trpm3-channels-increases-interleukin-8-gene-promoter-activity-involving-ap-1-and-extracellular-signal-regulated-protein-kinase
#5
Sandra Rubil, Andrea Lesch, Naofumi Mukaida, Gerald Thiel
Stimulation of Ca(2+) permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells...
October 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28977001/microrna-30b-controls-endothelial-cell-capillary-morphogenesis-through-regulation-of-transforming-growth-factor-beta-2
#6
Grant A Howe, Kayla Kazda, Christina L Addison
The importance of microRNA (miRNA) to vascular biology is becoming increasingly evident; however, the function of a significant number of miRNA remains to be determined. In particular, the effect of growth factor regulation of miRNAs on endothelial cell morphogenesis is incomplete. Thus, we aimed to identify miRNAs regulated by pro-angiogenic vascular endothelial growth factor (VEGF) and determine the effects of VEGF-regulated miRNAs and their targets on processes important for angiogenesis. Human umbilical vein endothelial cells (HUVECs) were thus stimulated with VEGF and miRNA levels assessed using microarrays...
2017: PloS One
https://www.readbyqxmd.com/read/28918037/a-novel-pak1-atf2-mir-132-signaling-axis-is-involved-in-the-hematogenous-metastasis-of-gastric-cancer-cells
#7
Funan Liu, Zhenguo Cheng, Xiaodong Li, Yanshu Li, Hongyan Zhang, Jiabin Li, Furong Liu, Huimian Xu, Feng Li
We, along with others, have shown previously that P21-activated kinase 1 (Pak1) plays a pivotal role in gastric cancer progression and metastasis. However, whether Pak1 controls gastric cancer metastasis by regulating microRNAs (miRNAs) has never been explored. Here, we report a novel mechanism of Pak1 in tumor metastasis. A detailed examination revealed that Pak1 interacts with and phosphorylates the serine 62 residue of ATF2 and then blocks its translocation into the nucleus. We also confirmed that ATF2 binds to the promoter of miR-132 and tightly regulates its transcription, thus explaining the regulatory mechanism of miR-132 by Pak1...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916425/p38mapk-family-isoform-p38%C3%AE-and-activating-transcription-factor-2-are-associated-with-the-malignant-phenotypes-and-poor-prognosis-of-patients-with-ovarian-adenocarcinoma
#8
Wan-Juan Song, Yu Dong, Cheng Luo, Yuan-Yuan Chen
This study was to identify the biomarkers for the malignancy and poor prognosis in patients with ovarian cancer. The protein expression of p38MAPK family isoform p38α (p38α) and activating transcription factor 2 (ATF2) was measured in 120 ovarian serous adenocarcinomas and 34 normal fallopian tubes using immunohistochemistry. Stable OV-90 cells expressing p38α and ATF2 inhibitor were established using shRNA lentivirus. Cell proliferation, invasion, and migration were analyzed in vitro. Tumor growth and chemosensitivity were investigated in xenograft tumor models...
October 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28887384/constitutive-activation-of-p46jnk2-is-indispensable-for-c-ebp%C3%AE-induction-in-the-initial-stage-of-adipogenic-differentiation
#9
Joji Kusuyama, Tomokazu Ohnishi, Kenjiro Bandow, Muhammad Subhan Amir, Kaori Shima, Ichiro Semba, Tetsuya Matsuguchi
Adipogenic differentiation plays a vital role in energy homeostasis and endocrine system. Several transcription factors, including peroxisome proliferator-activated receptor gamma 2 and CCAAT-enhancer-binding protein (C/EBP) α, β, and δ, are important for the process, whereas the stage-specific intracellular signal transduction regulating the onset of adipogenesis remains enigmatic. Here, we explored the functional role of c-jun N-terminal kinases (JNKs) in adipogenic differentiation using in vitro differentiation models of 3T3-L1 cells and primary adipo-progenitor cells...
October 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28836366/lipoteichoic-acid-upregulates-plasminogen-activator-inhibitor-1-expression-in-parapneumonic-effusions
#10
Kai-Ling Lee, Wei-Lin Chen, Ray-Jade Chen, Kevin S Lai, Chi-Li Chung
BACKGROUND AND OBJECTIVE: Parapneumonic effusion (PPE) is commonly caused by Gram-positive bacteria (GPB) and often presents with pleural loculation, which is characterized by overproduction of plasminogen activator inhibitor (PAI)-1. Lipoteichoic acid (LTA), a surface adhesion molecule of GPB, binds to the pleural mesothelium and triggers inflammation. However, the effects of LTA on PAI-1 expression in PPE and underlying mechanisms remain unclear. METHODS: Thirty consecutive patients with PPE were enrolled, including uncomplicated culture negative (CN, n = 11), Gram-negative bacteria (GNB, n = 7) and GPB (n = 12) groups stratified by pleural fluid characteristics and bacteriology, and the effusion PAI-1 levels were measured...
August 23, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28833446/necrotic-cell-death-occur-via-jnk-pathway-with-the-activity-of-transcription-factor-c-jun-by-4-mc-in-ins-1-cell-line
#11
Ayse Karatug Kacar, Sehnaz Bolkent
In this study, it was aimed to determine the doses of 4-methylcatechol causing cell death in rat insulinoma β-cells (INS-1), to find out the type of cellular death at these doses, and to investigate the molecular mechanism of cellular death occurring. More necrotic cells were observed than apoptosis with the administration of 350, 400, and 450 μM 4-methylcatechol. Lactate dehydrogenase levels, reactive oxygen species, mitochondrial potential loss, ATP and GTP losses increased at these doses. The JNK and ERK cellular pathway were screened...
August 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#12
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28723567/cold-inducible-sirt6-regulates-thermogenesis-of-brown-and-beige-fat
#13
Lu Yao, Xiaona Cui, Qi Chen, Xiaoying Yang, Fude Fang, Jun Zhang, Guoqing Liu, Wanzhu Jin, Yongsheng Chang
Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological "whitening" of brown fat, reduced oxygen (O2) consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28641113/enhanced-functional-genomic-screening-identifies-novel-mediators-of-dual-leucine-zipper-kinase-dependent-injury-signaling-in-neurons
#14
Derek S Welsbie, Katherine L Mitchell, Vinod Jaskula-Ranga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E Martin, Ping-Wu Zhang, Yan Ge, Yukan Duan, John Fuller, Byung-Jin Kim, Eman Hamed, Xitiz Chamling, Lei Lei, Iain D C Fraser, Ze'ev A Ronai, Cynthia A Berlinicke, Donald J Zack
Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#15
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#16
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
July 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28618963/noxin-promotes-proliferation-of-breast-cancer-cells-via-p38-atf2-signaling-pathway
#17
Xiupeng Zhang, Yong Zhang, Chuifeng Fan, Liang Wang, Yang Liu, Ailin Li, Guiyang Jiang, Haijing Zhou, Lin Cai, Yuan Miao
Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#18
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, ChiHu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509555/differential-phosphoproteomic-analysis-of-recombinant-chinese-hamster-ovary-cells-following-temperature-shift
#19
Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes, including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis, and signal transduction. However, to date, little work has been carried out on the phosphoproteome in CHO cells. In this study we have carried out a large scale differential phosphoproteomic analysis of recombinant CHO cells following a reduction of culture temperature (temperature shift)...
June 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#20
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We reported recently that the reprogramming factor Krüppel-like factor 4 (KLF4) has a tumor-suppressive function in children with T-ALL...
September 2017: Experimental Hematology
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