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phosphatase protein 1

Jing Wu, Wei-Wei Tao, Dan-Yang Chong, Shan-Shan Lai, Chuang Wang, Qi Liu, Tong-Yu Zhang, Bin Xue, Chao-Jun Li
Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Muhmmad Omar-Hmeadi, Nikhil Gandasi, Sebastian Barg
Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution TIRF imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules...
March 14, 2018: Traffic
Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs...
March 14, 2018: Science Translational Medicine
Cheng-Han Yu, Chi-Chi Chou, Der-Yen Lee, Kay-Hooi Khoo, Geen-Dong Chang
Phenyl vinyl sulfone (PVS) and phenyl vinyl sulfonate (PVSN) inactivate protein tyrosine phosphatases (PTPs) by mimicking the phosphotyrosine structure and providing a Michael addition acceptor for the active-site cysteine residue of PTPs, thus forming covalent adducts between PVS (or PVSN) and PTPs. We developed a specific antiserum against PVS. This antiserum can be used in general antibody-based assays such as immunoblotting, immunofluorescence staining, and immunoprecipitation. Target identification through immunoprecipitation and mass spectrometry analysis reveals potential targets of PVS, mostly proteins with reactive cysteine residues or low-pKa cysteine residues that are prone to reversible redox modifications...
March 14, 2018: Bioscience Reports
Philippe A Melas, Johanna S Qvist, Matteo Deidda, Chirag Upreti, Ya Bin Wei, Fabrizio Sanna, Walter Fratta, Maria Scherma, Paola Fadda, Denise B Kandel, Eric R Kandel
Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus...
March 13, 2018: Cell Reports
Avshalom Leibowitz, Ariel Bier, Mayan Gilboa, Edna Peleg, Iris Barshack, Ehud Grossman
Recent data indicate that artificial sweeteners (AS) may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD) on glucose metabolism and insulin resistance (IR) in Sprague-Dawley (SD) rats. SD rats were fed either regular chow, chow with saccharin (Sac) (0.1 mg/mL) placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg) levels were measured upon completion. A homeostatic model assessment (HOMA)-IR index was used to determine insulin resistance...
March 12, 2018: Nutrients
Seung Min Jung, Jaeseon Lee, Seung Ye Baek, Juhyun Lee, Se Gwang Jang, Seung-Min Hong, Jin-Sil Park, Mi-La Cho, Sung-Hwan Park, Seung-Ki Kwok
This study aimed to evaluate the therapeutic effect of fraxinellone on inflammatory arthritis and identify the underlying mechanisms. Fraxinellone (7.5 mg/kg) or a vehicle control was injected into mice with collagen-induced arthritis (CIA). The severity of arthritis was evaluated clinically and histologically. The differentiation of CD4⁺ T cells and CD19⁺ B cells was investigated in the presence of fraxinellone. Osteoclastogenesis after fraxinellone treatment was evaluated by staining with tartrate-resistant acid phosphatase (TRAP) and by measuring the mRNA levels of osteoclastogenesis-related genes...
March 13, 2018: International Journal of Molecular Sciences
Takenobu Ishii, Montserrat Ruiz-Torruella, Atsushi Ikeda, Satoru Shindo, Alexandru Movila, Hani Mawardi, Abdullah Albassam, Rayyan A Kayal, Ayman A Al-Dharrab, Kenji Egashira, Wichaya Wisitrasameewong, Kenta Yamamoto, Abdulghani I Mira, Kenji Sueishi, Xiaozhe Han, Martin A Taubman, Takeshi Miyamoto, Toshihisa Kawai
Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. Contrast to DC-STAMP of which knockout (KO) mice show osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Masaki Kobayashi, Douglas W Zochodne
Diabetic polyneuropathy (DPN) continues to be generally considered as a "microvascular" complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, may be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of mRNA changes related to declines in structural proteins, increases in heat shock protein (HSP), increases in the receptor for advanced glycation endproducts (RAGE), declines in growth factor signaling and other changes...
March 13, 2018: Journal of Diabetes Investigation
Zuo Peng Li, Hyeong-Hwan Lee, Zia Uddin, Yeong Hun Song, Ki Hun Park
Four new caged xanthones (1-4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1-6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1-6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer...
March 7, 2018: Bioorganic Chemistry
Jiang Qiu, Gang Huang, Ning Na, Lizhong Chen
Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)‑214‑5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed...
March 9, 2018: Molecular Medicine Reports
Weiqing Qian, Yan Su, Yajie Zhang, Nianwei Yao, Nin Gu, Xu Zhang, Hong Yin
Osteoporosis is a serious public health problem and icariin (ICA) is the active component of the Epimedium sagittatum, a traditional Chinese medicinal herb. The present study aimed to investigate the effects and underlying mechanisms of ICA as a potential therapy for osteoporosis. Calvaria osteoblasts were isolated from newborn rats and treated with ICA. Cell viability, apoptosis, alkaline phosphatase activity and calcium deposition were analyzed. Bioinformatics analyses were performed to identify differentially expressed proteins (DEPs) in response to ICA treatment...
March 9, 2018: Molecular Medicine Reports
Soo Ji Woo, Na Young Kim, Shin Hu Kim, Sang Jung Ahn, Jung Soo Seo, Sung Hee Jung, Joon Ki Chung
Trichlorfon is a moderately toxic organophosphate pesticide that is widely used in aquaculture. This study investigated the effects of trichlorfon on hematological parameters, biochemical factors, and stress reaction in Cyprinus carpio L. The fish were exposed to acute concentrations of trichlorfon (0, 0.5, 1.0, 2.0, and 4.0 mg L-1 ) at 25 °C and 15 °C for 1 and 2 weeks, after which several parameters were evaluated to assess the effects of the pesticide. Significant decreases were observed in red blood cell (RBC) Count, hemoglobin (Hb) level, hematocrit (Ht), and plasma protein levels after each exposure period...
March 9, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Sylwia Kedziora, Vamsi K Gali, Rosemary H C Wilson, Kate R M Clark, Conrad A Nieduszynski, Shin-Ichiro Hiraga, Anne D Donaldson
The Rif1 protein negatively regulates telomeric TG repeat length in the budding yeast Saccharomyces cerevisiae, but how it prevents telomere over-extension is unknown. Rif1 was recently shown to control DNA replication by acting as a Protein Phosphatase 1 (PP1)-targeting subunit. Therefore, we investigated whether Rif1 controls telomere length by targeting PP1 activity. We find that a Rif1 mutant defective for PP1 interaction causes a long-telomere phenotype, similar to that of rif1Δ cells. Tethering PP1 at a specific telomere partially substitutes for Rif1 in limiting TG repeat length, confirming the importance of PP1 in telomere length control...
February 26, 2018: Nucleic Acids Research
Jie Zhang, Tatsunori Sasaki, Wei Li, Kazuya Nagata, Koji Higai, Feng Feng, Jian Wang, Maosheng Cheng, Kazuo Koike
Considerable attention has been paid to protein tyrosine phosphatase 1B (PTP1B) inhibitors as a potential therapy for diabetes, obesity, and cancer. Ten caffeoylquinic acid derivatives (1-10) from leaves of Artemisia princeps Pamp. (Asteraceae) were identified as natural PTP1B inhibitors. Among them, chlorogenic acid (3) showed the most potent inhibitory activity (IC50 11.1 μM). Compound 3 was demonstrated to be a noncompetitive inhibitor by a kinetic analysis. Molecular docking simulation suggested that compound 3 bound to the allosteric site of PTP1B...
March 6, 2018: Bioorganic & Medicinal Chemistry Letters
Hyewon Shin, Minzhen He, Zhi Yang, Yong Heui Jeon, Jessica Pfleger, Danish Sayed, Maha Abdellatif
The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit...
March 7, 2018: Biochimica et Biophysica Acta
Jeong-Min Hong, Sun-Mee Lee
AIMS: Heme oxygenase-1 (HO-1), an endogenous cytoprotective enzyme, is reported that can be localized in mitochondria under stress, contributing to preserve mitochondrial function. Mitochondrial quality control (QC) is essential to cellular health and recovery linked with redox homeostasis. Recent studies reported that phosphoglycerate mutase family member (PGAM) 5, a mitochondria-resident phosphatase, plays critical role in mitochondrial homeostasis. Therefore, we aim to investigate cytoprotective mechanisms of HO-1 in I/R-induced hepatic injury focusing on mitochondrial QC associated with PGAM5 signaling...
March 7, 2018: Life Sciences
Lin Zhou, Lu Wang, Shuju Bai, Shu Xing, Wannan Li, Junfeng Ma, Xueqi Fu
Low molecular weight protein tyrosine phosphatase (LMW-PTP) is highly conserved across almost all living organisms and is involved in the modulation of a number of cellular proteins related to important signaling pathways. In this study, we isolated lmwptp (Y94H6A.7) of Caenorhabditis elegans, the homolog of human ACP1, and set up an effective feeding-based RNA interference (RNAi) knockdown against this gene. We found that knockdown of lmwptp decreased damage associated with heat shock, oxidative stress and UV irradiation in wild-type worms, however, its deficiency didn't further reduce the stress resistance of hsf-1 or daf-16 mutants and didn't further increase the stress sensitivity associated with age-1, akt-1 or akt-2 mutants, but it enhanced the stress resistance of daf-2 mutants...
March 7, 2018: International Journal of Biological Macromolecules
Jong-Woon Shin, Sae-Bom Kwon, Yesol Bak, Sang-Ku Lee, Do-Young Yoon
The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53...
March 28, 2018: Science China. Life Sciences
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