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FEBS Open Bio

Yoji Kyotani, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Mai Makino, Shin Takasawa, Masanori Yoshizumi
Patients with obstructive sleep apnea (OSA) experience repetitive episodes of desaturation and resaturation of blood oxygen (known as intermittent hypoxia or IH), during sleep. We showed previously that IH induced excessive proliferation of rat vascular smooth muscle cells through upregulation of members of the epidermal growth factor family, especially epiregulin (EREG), and the erbB2 receptor. In this study, we exposed human coronary artery smooth muscle cells to IH and found that IH significantly increased the expression of EREG...
May 2018: FEBS Open Bio
Zhehao Dai, Haoyu Tang, Yue Pan, Junquan Chen, Yongping Li, Jun Zhu
Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pathways and important modules during the exposure of human osteosarcoma cells to sorafenib, data for gene expression profiles ( were downloaded from the GEO database...
May 2018: FEBS Open Bio
Elizabeth Vleeskens, Ronald J Clarke
The sodium potassium pump (Na+ ,K+ -ATPase) shows a high selectivity for K+ over Na+ binding from the extracellular medium. To understand the K+ selectivity in the presence of a high concentration of competing Na+ ions requires consideration of more than just ion binding affinities. Here, equilibrium-based calculations of the extracellular occupation of the Na+ ,K+ -ATPase transport sites by Na+ and K+ are compared to fluxes through Na+ and K+ transport pathways. The results show that, under physiological conditions, there is a 332-fold selectivity for pumping of K+ from the extracellular medium into the cytoplasm relative to Na+ , whereas equilibrium calculations alone predict only a 7...
May 2018: FEBS Open Bio
Jiye Kim, Yoon-Hee Kwon, Chu-Sook Kim, Thai H Tu, Byung-Sam Kim, Yeonsoo Joe, Hun T Chung, Tsuyoshi Goto, Teruo Kawada, Taesun Park, Myung-Sook Choi, Min-Seon Kim, Rina Yu
Obesity-induced inflammation occurs not only in peripheral tissues but also in areas of the central nervous system. Glial cells such as astrocytes and microglia play crucial roles in obesity-related hypothalamic inflammation, leading to the derangement of energy metabolism and neurodegenerative pathologies. Here, we show that the interaction of 4-1BB/4-1BBL between lipid-laden astrocytes/microglia promotes hypothalamic inflammation in obesity. Stimulation of 4-1BB, a member of the TNF receptor superfamily, and/or its ligand 4-1BBL on astrocytes and/or microglia with a specific agonist resulted in activation of the inflammatory signaling pathway and enhanced production of inflammatory mediators...
May 2018: FEBS Open Bio
Tadashi Kato, Atsushi Yamada, Mikiko Ikehata, Yuko Yoshida, Kiyohito Sasa, Naoko Morimura, Akiko Sakashita, Takehiko Iijima, Daichi Chikazu, Hiroaki Ogata, Ryutaro Kamijo
Nephronectin (Npnt), an extracellular matrix protein, is a ligand for integrin α8β1 and is involved in the development of various organs, such as the kidneys, bones, liver, and muscles. Previously, we found that Npnt expression was inhibited by various cytokines including transforming growth factor-β (Tgf-β) and oncostatin M (Osm). Fibroblast growth factor (Fgf)-2, otherwise known as basic Fgf, also plays important roles in skeletal development and postnatal osteogenesis. In this study, Npnt expression was found to be suppressed by Fgf-2 in MC3T3-E1 cells, an osteoblast-like cell line, in a dose- and time-dependent manners...
May 2018: FEBS Open Bio
Huan Zhao, Xuan Zhang, Zhifeng Han, Zhenqi Wang, Yao Wang
A recent study demonstrated that circulating levels of IgG antibodies against linear peptide antigens derived from baculoviral IAP repeat-containing protein 5 isoform 2 (BIRC5) and myc proto-oncogene protein (MYC) were significantly increased in nonsmall cell lung cancer (NSCLC). This study was undertaken to replicate this initial work in an independent sample. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma IgG antibodies for three linear peptide antigens derived from BIRC5a, BIRC5b, and MYC in 211 patients with NSCLC and 200 control subjects...
May 2018: FEBS Open Bio
Maria H Jäntti, Virpi Talman, Kati Räsänen, Ilari Tarvainen, Hannu Koistinen, Raimo K Tuominen
Prostate cancer is one of the most common cancers in men. Although it has a relatively high 5-year survival rate, development of resistance to standard androgen-deprivation therapy is a significant clinical problem. Therefore, novel therapeutic strategies are urgently needed. The protein kinase C (PKC) family is a putative prostate cancer drug target, but so far no PKC-targeting drugs are available for clinical use. By contrast to the standard approach of developing PKC inhibitors, we have developed isophthalate derivatives as PKC agonists...
May 2018: FEBS Open Bio
Yusuke Ito, Yasuhiro Maejima, Natsuko Tamura, Yuka Shiheido-Watanabe, Masanori Konishi, Takashi Ashikaga, Kenzo Hirao, Mitsuaki Isobe
5-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have beneficial effects in patients with heart failure (HF), regardless of serum cholesterol levels. However, their synergic effects with angiotensin II receptor blocker (ARB) remain to be established. We assessed the existence and potential underlying mechanisms of the effects of combined ARB [losartan (LOS)] and statin [simvastatin (SIM)] on cardiac function in rats and mice with load-induced HF. Salt-loaded Dahl salt-sensitive (DS) rats were treated with vehicle, LOS, SIM, or LOS + SIM for 8 weeks...
May 2018: FEBS Open Bio
Jonathan Parrilla, Cécile Gaillard, Jérémy Verbeke, Mickaël Maucourt, Radoslav A Aleksandrov, Florence Thibault, Pierrette Fleurat-Lessard, Yves Gibon, Dominique Rolin, Rossitza Atanassova
A novel biological model was created for the comparison of grapevine embryogenic cells (EC) and nonembryogenic cells (NEC) sharing a common genetic background but distinct phenotypes, when cultured on their respective most appropriate media. Cytological characterization, 1 H-NMR analysis of intracellular metabolites, and glycolytic enzyme activities provided evidence for the marked metabolic differences between EC and NEC. The EC were characterized by a moderate and organized cell proliferation, coupled with a low flux through glycolysis, high capacity of phosphoenolpyruvate carboxylase and glucokinase, and high oxygen consumption...
May 2018: FEBS Open Bio
Jesper Torbøl Pedersen, Tamara Kanashova, Gunnar Dittmar, Michael Palmgren
The yeast plasma membrane H+ -ATPase Pma1p is a P-type ATPase that energizes the yeast plasma membrane. Pma1p exists in two activation states: an autoinhibited basal state and an activated state. Here we show that functional and stable Pma1p can be purified in native form and reconstituted in artificial liposomes without altering its activation state. Acetylated tubulin has previously been reported to maintain Pma1p in the basal state but, as this protein was absent from the purified preparations, it cannot be an essential component of the autoinhibitory mechanism...
May 2018: FEBS Open Bio
Changyu Chen, Jun Lei, Qiang Zheng, Sheng Tan, Keshuo Ding, Changjun Yu
Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly(rC) binding protein 2 (PCBP2) is an RNA-binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues...
May 2018: FEBS Open Bio
Graeme P Sullivan, Pavel B Davidovich, Sylvia Sura-Trueba, Ekaterina Belotcerkovskaya, Conor M Henry, Danielle M Clancy, Anna Zinoveva, Tazhir Mametnabiev, Alexander V Garabadzhiu, Seamus J Martin
IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis...
May 2018: FEBS Open Bio
Xiaofeng Lai, Weipeng Su, Hu Zhao, Shunliang Yang, Tengyue Zeng, Weizhen Wu, Dong Wang
Most patients with prostate cancer will eventually develop the castration-resistant form characterised by metastasis. Cytoskeleton constituents, including F-actin, play important roles in maintaining epithelial integrity and their disruption is a major cause of cancer progression. We previously showed that scinderin (SCIN), an important regulator of F-actin organisation, is highly expressed in poorly differentiated cancer tissues. This study aimed to explore the mechanism of its regulation of cell proliferation...
May 2018: FEBS Open Bio
Xiaona Wang, Qiang Xue, Liangliang Wu, Baogui Wang, Han Liang
Dasatinib, a tyrosine kinase inhibitor, has been approved for first-line treatment of leukemia and has also been evaluated for use in numerous other cancers. However, its role in gastric cancer (GC) remains unclear. Therefore, the aim of this study was to investigate how dasatinib suppresses the growth of GC cells and interacts with chemotherapeutic drugs. The results showed that, in the presence of dasatinib, proliferation of GC cells decreased and apoptosis increased, and that Fas-associated death domain protein and caspase-8 are essential to dasatinib-induced cell apoptosis in GC...
May 2018: FEBS Open Bio
Rui Ni, Lingfei Luo
Histidyl-tRNA synthetase (Hars) catalyzes the ligation of histidine residues to cognate tRNA. Here, we demonstrate a noncanonical function of Hars in vascular development in zebrafish. We obtained a novel zebrafish cq34 mutant which exhibited hyperbranching of cranial and intersegmental blood vessels 48 h after fertilization. The gene responsible for this phenotype was identified as hars . We found the increased expression of cdh5 and vegfa in the hars cq34 mutant. Knockdown of cdh5 in the mutant reduced disordered connections of the hindbrain capillaries...
May 2018: FEBS Open Bio
Ilaria Baglivo, Luciano Pirone, Gaetano Malgieri, Roberto Fattorusso, Roy Martin Roop Ii, Emilia Maria Pedone, Paolo Vincenzo Pedone
The protein MucR from Brucella spp. is involved in the expression regulation of genes necessary for host interaction and infection. MucR is a member of the Ros/MucR family, which comprises prokaryotic zinc-finger proteins and includes Ros from Agrobacterium tumefaciens and the Ml proteins from Mesorhizobium loti . MucR from Brucella spp. can regulate the expression of virulence genes and repress its own gene expression. Despite the well-known role played by MucR in the repression of its own gene, no target sequence has yet been identified in the mucR promoter gene...
April 2018: FEBS Open Bio
Vishnu Hosur, Michelle L Farley, Lisa M Burzenski, Leonard D Shultz, Michael V Wiles
The epidermal growth factor (EGF)-receptor ligand amphiregulin (AREG) is a potent growth factor implicated in proliferative skin diseases and in primary and metastatic epithelial cancers. AREG, synthesized as a propeptide, requires conversion to an active peptide by metalloproteases by a process known as ectodomain shedding. Although (ADAM17) a disintegrin and metalloprotease 17 is a key sheddase of AREG, ADAM8-, ADAM15-, and batimastat (broad metalloprotease inhibitor)-sensitive metalloproteases have also been implicated in AREG shedding...
April 2018: FEBS Open Bio
Martin Jabůrek, Jan Ježek, Petr Ježek
Mitochondrial uncoupling protein-2 (UCP2) mediates free fatty acid (FA)-dependent H+ translocation across the inner mitochondrial membrane (IMM), which leads to acceleration of respiration and suppression of mitochondrial superoxide formation. Redox-activated mitochondrial phospholipase A2 (mt-iPLA2γ) cleaves FAs from the IMM and has been shown to acts in synergy with UCP2. Here, we tested the mechanism of mt-iPLA2γ-dependent UCP2-mediated antioxidant protection using lipopolysaccharide (LPS)-induced pro-inflammatory and pro-oxidative responses and their acute influence on the overall oxidative stress reflected by protein carbonylation in murine lung and spleen mitochondria and tissue homogenates...
April 2018: FEBS Open Bio
Tomomi Kubota, Osamu Tani, Tomohiko Yamaguchi, Ichiji Namatame, Hitoshi Sakashita, Koji Furukawa, Kazuhiko Yamasaki
Dihydroorotate dehydrogenase (DHODH) is a flavin-binding enzyme essential for pyrimidine biosynthesis, which converts dihydroorotate to orotate. Three-dimensional structures of cytosolic DHODH of parasitic protozoa are of interest in drug discovery for neglected tropical diseases, especially because these enzymes possess significantly different structural and functional properties from the membrane-associated human enzyme. The existing crystal structures of the flavin mononucleotide (FMN)-bound DHODHs reveal a number of interactions stabilizing FMN...
April 2018: FEBS Open Bio
Yuriko Wada, Kosuke Takemura, Padmaja Tummala, Keisuke Uchida, Keisuke Kitagaki, Asuka Furukawa, Yuuki Ishige, Takashi Ito, Yukichi Hara, Takashige Suzuki, Hitomi Mimuro, Philip G Board, Yoshinobu Eishi
Infection with Helicobacter pylori is known to decrease the level of glutathione in gastric epithelial cells and increase the production of reactive oxygen species (ROS), which can lead to DNA damage and the development of gastric cancer. Cation transport regulator 1 (CHAC1) has γ-glutamylcyclotransferase activity that degrades glutathione. We found that cagA -positive H. pylori infection triggered CHAC1 overexpression in human gastric epithelial (AGS) cells leading to glutathione degradation and the accumulation of ROS...
April 2018: FEBS Open Bio
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