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https://www.readbyqxmd.com/read/29054108/increase-in-pro-apoptotic-activity-of-inhibitory-pas-domain-protein-via-phosphorylation-by-mk2
#1
Shuya Kasai, Mary Jane Elizabeth Richardson, Satoru Torii, Ken-Ichi Yasumoto, Hiroki Shima, Kazuhiko Igarashi, Ken Itoh, Kazuhiro Sogawa, Kazutaka Murayama
Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates hypoxic gene expression and exerts pro-apoptotic activity by preventing pro-survival activity of Bcl-xL and its related factors. Pro-apoptotic activity of IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in neuronal degeneration in an experimental mouse model of Parkinson's disease. The current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated protein kinase 2 (MK2 or MAPKAPK2) enhances the pro-apoptotic function of IPAS...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29052963/deficiency-of-p38%C3%AE-in-macrophage-ameliorates-d-galactosamine-tnf-%C3%AE-induced-acute-liver-injury-in-mice
#2
Jiao Liu, Shengjie Zhang, Hongchao Cao, Hui Wang, Chao Sun, Shengnan Liu, Shuxian Yu, Yan Li, Wei Liu, Hui Wang, Jingjing Jiang, Hao Ying
Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells and promoting hepatocyte proliferation. Understanding the role of macrophage in the pathogenesis of liver injury will help pave the way to future therapeutics. Here we investigated whether macrophage p38α plays a regulatory role in the tissue repair following a GalN/TNF-α-induced acute liver injury. We found that macrophage p38α deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29052919/oamdp-a-novel-podophyllotoxin-derivative-induces-apoptosis-cell-cycle-arrest-and-autophagy-in-hepatoma-hepg2-cells
#3
Jie Ren, Yu Liu, Lixia Li, Yuexin Zhao, Zhongyu Li, Chao Wu, Lin Chen, Kun Hu
4β-(1,3,4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin (OAMDP), a novel podophyllotoxin derivative, has demonstrated potent anti-tumor activity with significant cytotoxic effect. Here we report the anti-proliferative effect of OAMDP, for which OAMDP could suppress the proliferation of HepG2 cells (human hepatoma cell line) in a dose- and time-dependent manner. After treating with OAMDP, cell apoptosis was confirmed by Annexin V-FITC/PI double staining assay. Furthermore, flow cytometry analysis revealed the loss of mitochondrial membrane potential and the increase of intracellular reactive oxygen species in HepG2 cells...
October 20, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29052381/-pharmacodynamic-mechanism-of-modified-ganlu-yaoyu-san-intreatment-of-rheumatoid-arthritis-based-on-mapk-signaling-pathway
#4
Fang Zuo, Ting Wei, Dong Tong, Yi Zhang, Xiao-Rui Chen, Yong Zeng
According to the findings, modified Ganlu Yaoyu San has a good anti-inflammatory activity, and can significantly alleviate the degree of arthritis. Its therapeutic effect for rheumatoid arthritis may be related to the regulation of MAPK pathway of synovial cells. In the study, the rat adjuvant arthritis(AA) model was established to further investigate the pharmacodynamic mechanism for regulating MAPK pathway of synovial cells. Enzyme-linked immune assay was used to determine the serum TNF-α level of AA rats administered with drug for two weeks, synovial tissue protein kinases ERK1/2 and p38 content were determined by immunohistochemistry, synovial tissue JNK1, ERK1, p38 gene(mRNA) expression were detected with fluorescence quantitative PCR(RT-PCR) method...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29052270/crystal-structure-of-the-human-dual-specificity-phosphatase-1-catalytic-domain
#5
Rajesh Gumpena, George T Lountos, Sreejith Raran-Kurussi, Joseph E Tropea, Scott Cherry, David S Waugh
The dual specificity phosphatase DUSP1 was the first mitogen activated protein kinase phosphatase (MKP) to be identified. It dephosphorylates conserved tyrosine and threonine residues in the activation loops of mitogen activated protein kinases ERK2, JNK1 and p38-alpha. Here, we report the crystal structure of the human DUSP1 catalytic domain at 2.49 Å resolution. Uniquely, the protein was crystallized as an MBP fusion protein in complex with a monobody that binds to MBP. Sulfate ions occupy the phosphotyrosine and putative phosphothreonine binding sites in the DUSP1 catalytic domain...
October 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29051621/vector-independent-transmembrane-transport-of-oligodeoxyribonucleotides-involves-p38-mitogen-activated-protein-kinase-phosphorylation
#6
Minyuan Peng, Yanming Li, Jian Zhang, Yong Wu, Xiaoyang Yang, Ye Lei, Mao Ye, Jing Liu, Xu Han, Yijin Kuang, Xielan Zhao, Fangping Chen
The main roles of equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs) are to transfer single nucleosides and analogues for the nucleic acid salvage pathway. Oligodeoxyribonucleotides (ODNs) can be transported into the cytoplasm or nucleus of cells under certain conditions. Among ODNs composed of a single type of nucleotide, the transport efficiency differs with the length and nucleotide composition of the ODNs and varies in different types of leukaemia cells; among the 5 tested random sequence ODNs and 3 aptamers with varying sequences, the data showed that some sequences were associated with significantly higher transport efficiency than others...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051186/distinct-roles-of-intracellular-heat-shock-protein-70-hsp70-in-maintaining-gastrointestinal-homeostasis
#7
Yunwei Wang, Fanfei Lin, Xiaorong Zhu, Vanessa A Leone, Sushila R Dalal, Yun Tao, Jeannette S Messer, Eugene B Chang
The inducible heat shock protein 70 (Hsp70) is both cytoprotective and immunomodulatory, potentially accounting for its critical role in maintaining gastrointestinal homeostasis. When levels are reduced in conditions like inflammatory bowel diseases (IBD), loss of function contributes to the severity and chronicity of these diseases, although through which cell types and mechanisms remains unclear. Here, the role of Hsp70-mediated intestinal epithelial protection and immune regulation in experimental colitis was examined by using a villin-promoter driven Hsp70 transgene in the TNBS and DSS models and in IL10/Hsp70 double knockout (IL10(-/-)/Hsp70(-/-)) mice...
October 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29050978/chrysin-attenuates-atopic-dermatitis-by-suppressing-inflammation-of-keratinocytes
#8
Jin Kyeong Choi, Yong Hyun Jang, Soyoung Lee, Sang-Rae Lee, Young-Ae Choi, Meiling Jin, Jung Ho Choi, Jee Hun Park, Pil-Hoon Park, Hyukjae Choi, Taeg Kyu Kwon, Dongwoo Khang, Sang-Hyun Kim
We previously reported the inhibitory effect of chrysin, a natural flavonoid plentifully contained in propolis, vegetables and fruits, on the mast cell-mediated allergic reaction. In this study, we evaluated the effect of chrysin on atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae extract, DFE) to the ears. Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions...
October 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29050670/ginseng-polysaccharide-serves-as-a-potential-radiosensitizer-through-inducing-apoptosis-and-autophagy-in-the-treatment-of-osteosarcoma
#9
Xiao-Yu Zhang, Ke Sun, Qi Zhu, Tao Song, Yang Liu
Recent studies have confirmed that the combined use of anti-cancer drugs with ionizing radiation (IR) could improve the sensitivity of osteosarcoma (OS) cells. Therefore, it is necessary to identify potential effective drugs for the enhancement of IR-radiosensitivity. In the current study, we found that 20, 10, 5, and 1 μM of ginseng polysaccharide (GPS) significantly suppressed MG-63 cell viability with or without γ-ray radiation in a dose- and time-dependent manner. Strikingly, 20 μM of GPS combined with 5 Gy treatment suppressed colony formation capacity by nearly 13...
November 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29049722/a-ppar-gamma-agonist-rosiglitazone-suppresses-fibrotic-response-in-human-pterygium-fibroblasts-by-modulating-the-p38-mapk-pathway
#10
Selikem Abla Nuwormegbe, Joon Hyung Sohn, Sun Woong Kim
Purpose: Fibroblast activation may play an important role in pterygium progression. Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods: Profibrotic activation was induced by TGF-β1 in primary cultured human pterygium fibroblasts and the effect of rosiglitazone treatment on α-smooth muscle actin (α-SMA), and extra cellular matrix proteins synthesis was detected by western blotting, real-time PCR, immunostaining, and flow cytometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29048662/capsaicin-inhibits-proliferation-and-induces-apoptosis-in-osteosarcoma-cell-lines-via-the-mitogen%C3%A2-activated-protein-kinase-pathway
#11
Yuan Zhang, Xu Deng, Tao Lei, Chang Yu, Yang Wang, Guosheng Zhao, Xiaoji Luo, Ke Tang, Zhengxue Quan, Dianming Jiang
Capsaicin, a pungent molecular compound present in many hot peppers, exerts anticancer activities against various human cancer cell lines by inducing apoptosis. However, the effects of capsaicin on human osteosarcoma (OS) as well as the related mechanisms remain to be fully elucidated. In the present study, the anticancer effects of capsaicin on 3 human OS cell lines (MG63, 143B and HOS) were investigated. Various concentrations of capsaicin (50-300 µM) effectively decreased cell viability in all 3 OS cell lines in a dose-dependent manner...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048621/irisin-reverses-the-il-6-induced-epithelial-mesenchymal-transition-in-osteosarcoma-cell-migration-and-invasion-through-the-stat3-snail-signaling-pathway
#12
Gang Kong, Yunpeng Jiang, Xiujiang Sun, Zhilin Cao, Guodong Zhang, Zhongyuan Zhao, Yong Zhao, Qian Yu, Gong Cheng
As a novel discovered myokine, irisin is considered to be a promising candidate for the treatment of metabolic disorders and cancer. However, little is known about the anti-metastasic effect of irisin on osteosarcoma cells and its underlying mechanisms. In the present study, we aimed to explore the effect of irisin on the migration and invasion of osteosarcoma cells and the underlying mechanisms involved. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Then, by using scratch wound healing assay and Transwell assays, we evaluated migratory and invasive ability of the cells, respectively...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048616/the-receptor-for-activated-protein-kinase-c-promotes-cell-growth-invasion-and-migration-in-cervical-cancer
#13
Shan Liao, Songshu Xiao, Hongxiang Chen, Manying Zhang, Zhifang Chen, Yuehua Long, Lu Gao, Junyu He, Yanshan Ge, Wei Yi, Minghua Wu, Guiyuan Li, Yanhong Zhou
Cervical cancer is one of the most common malignant tumors in women all over the world. However, the exact etiology of cervical cancer remains unclear. The receptor for activated protein kinase C (RACK1) is reported to be involved in tumorigenesis and tumor progression. Besides, the prognostic value of RACK1 in several kinds of tumors has been identified. However, there are limited studies on the functional role of RACK1 in cervical cancer. In this study, we tested the expression level of RACK1 by immunohistochemistry and western blot technologies and find that it is upregulated in cervical cancer...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047459/protostemonine-effectively-attenuates-lipopolysaccharide-induced-acute-lung-injury-in-mice
#14
Ya-Xian Wu, Hui-Qiong He, Yun-Juan Nie, Yun-He Ding, Lei Sun, Feng Qian
Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine). Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 μmol/L) for 0.5 h and then challenged with LPS (0.1 μg/mL) for 24 h...
October 19, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29047406/loss-of-mkp-5-promotes-myofiber-survival-by-activating-stat3-bcl-2-signaling-during-regenerative-myogenesis
#15
Kisuk Min, Ahmed Lawan, Anton M Bennett
BACKGROUND: The mitogen-activated protein kinases (MAPKs) have been shown to be involved in regulating myofiber survival. In skeletal muscle, p38 MAPK and JNK are negatively regulated by MAPK phosphatase-5 (MKP-5). During muscle regeneration, MKP-5 is downregulated, thereby promoting p38 MAPK/JNK signaling, and subsequent repair of damaged muscle. Mice lacking MKP-5 expression exhibit enhanced regenerative myogenesis. However, the effect of MKP-5 on myofiber survival during regeneration is unclear...
October 18, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29047264/the-inactivation-of-erk1-2-p38-and-nf-kb-is-involved-in-the-down-regulation-of-osteoclastogenesis-and-function-by-a2b-adenosine-receptor-stimulation
#16
Bo Hyun Kim, Ju Hee Oh, Na Kyung Lee
A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis, but its regulatory mechanisms in osteoclast formation are less well-defined. Here, we demonstrate the effect of A2BAR stimulation on osteoclast differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived monocyte/macrophage (BMM) and RANKL increased A2BAR expression during osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and NF-κB by RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast differentiation...
October 17, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29046637/meclizine-prevents-ovariectomy-induced-bone-loss-and-inhibits-osteoclastogenesis-partially-by-upregulating-pxr
#17
Jiachao Guo, Weijin Li, Yingxing Wu, Xingzhi Jing, Junming Huang, Jiaming Zhang, Wei Xiang, Ranyue Ren, Zhengtao Lv, Jun Xiao, Fengjing Guo
Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29046388/the-early-dendritic-cell-signaling-induced-by-virulent-francisellatularensis-strain-occurs-in-phases-and-involves-the-activation-of-erks-and-p38-in-the-later-stage
#18
Ivo Fabrik, Marek Link, Daniela Putzova, Lenka Plzakova, Zuzana Lubovska, Vlada Philimonenko, Ivona Pavkova, Pavel Rehulka, Zuzana Krocova, Pavel Hozak, Marina Santic, Jiri Stulik
Dendritic cells (DCs) infected by Francisella tularensis are poorly activated and do not undergo classical maturation process. While reasons of such unresponsiveness are not fully understood, their impact on the priming of immunity is well appreciated. Previous attempts to explain the behavior of Francisella-infected DCs were hypothesis-driven and focused on events at later stages of infection. Here, we took an alternative unbiased approach by applying methods of global phosphoproteomics to analyze the dynamics of cell signaling in primary DCs during the first hour of infection by Francisella tularensis...
October 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29046299/high-content-screening-assay-based-discovery-of-paullones-as-novel-podocyte-protective-agents
#19
Ha Won Lee, Ehtesham Arif, Mehmet Mete Altintas, Kevin Quick, Shrey Maheshwari, Alexandra Plezia, Aqsa Mahmood, Jochen Reiser, Deepak Nihalani, Vineet Gupta
Podocyte dysfunction and loss is an early event and a hallmark of proteinuric kidney diseases. Podocyte's normal function is maintained via its unique cellular architecture that relies on an intracellular network of filaments, including filamentous actin (F-actin) and microtubules, that provides mechanical support. Damage to this filamentous network leads to changes in cellular morphology and results in podocyte injury, dysfunction, and death. Conversely, stabilization of this network protects podocytes and ameliorates proteinuria...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29046261/cinnamaldehyde-induces-fat-cell-autonomous-thermogenesis-and-metabolic-reprogramming
#20
Juan Jiang, Margo P Emont, Heejin Jun, Xiaona Qiao, Jiling Liao, Dong-Il Kim, Jun Wu
OBJECTIVE: Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment. METHODS: Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans...
September 1, 2017: Metabolism: Clinical and Experimental
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