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Moshe Shashar, Mostafa E Belghasem, Shinobu Matsuura, Joshua Walker, Sean Richards, Faisal Alousi, Keshab Rijal, Vijaya B Kolachalama, Mercedes Balcells, Minami Odagi, Kazuo Nagasawa, Joel M Henderson, Amitabh Gautam, Richard Rushmore, Jean Francis, Daniel Kirchhofer, Kumaran Kolandaivelu, David H Sherr, Elazer R Edelman, Katya Ravid, Vipul C Chitalia
Chronic kidney disease (CKD/uremia) remains vexing because it increases the risk of atherothrombosis and is also associated with bleeding complications on standard antithrombotic/antiplatelet therapies. Although the associations of indolic uremic solutes and vascular wall proteins [such as tissue factor (TF) and aryl hydrocarbon receptor (AHR)] are being defined, the specific mechanisms that drive the thrombotic and bleeding risks are not fully understood. We now present an indolic solute-specific animal model, which focuses on solute-protein interactions and shows that indolic solutes mediate the hyperthrombotic phenotype across all CKD stages in an AHR- and TF-dependent manner...
November 22, 2017: Science Translational Medicine
Zebin Chen, Lixia Xu, Tianhong Su, Zunfu Ke, Zhenwei Peng, Ning Zhang, Sui Peng, Qiuyang Zhang, Gengxun Liu, Guangyan Wei, Yu Guo, Minghui He, Ming Kuang
Stress-induced phosphoprotein 1 (STIP1) is an adaptor protein that bridges between HSP70 and HSP90 folding and a secretory protein which regulates malignant cell growth. However, the role of STIP1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found high expression of STIP1 in tumors was associated with worse overall survival (41.3 vs 62.7 months, P < 0.001) in 231 HCC patients. STIP1 was overexpressed in HCC tissues compared to adjacent non-tumor liver tissue (64.9% vs 4.0% P < 0.001), and serum STIP1 levels of HCC patients were elevated compared to healthy controls (P < 0...
November 4, 2017: Biochemical and Biophysical Research Communications
Yi-Wei Xu, Can-Tong Liu, Xin-Yi Huang, Li-Sheng Huang, Yu-Hao Luo, Chao-Qun Hong, Hai-Peng Guo, Li-Yan Xu, Yu-Hui Peng, En-Min Li
Esophageal squamous cell carcinoma (ESCC) remains one of the leading causes of cancer-related mortality around the world. The identification of novel serum biomarkers is required for early detection of ESCC. This study was designed to elucidate whether autoantibodies against STIP1 could be a diagnostic biomarker in ESCC. An enzyme-linked immunosorbent assay was performed to detect serum levels of STIP1 autoantibodies in a training cohort (148 ESCC patients and 111 controls) and a validation cohort (60 ESCC patients and 40 controls)...
2017: Disease Markers
Jeanelle Ariza, Jesus Hurtado, Haille Rogers, Raymond Ikeda, Michael Dill, Craig Steward, Donnay Creary, Judy Van de Water, Verónica Martínez-Cerdeño
An association between maternal IgG antibodies reactive against proteins in fetal brain and an outcome of autism in the child has been identified. Using a mouse model of prenatal intraventricular administration of autism-specific maternal IgG, we demonstrated that these antibodies produce behavioral alterations similar to those in children with ASD. We previously demonstrated that these antibodies bind to radial glial stem cells (RG) and observed an increase in the number of divisions of translocating RG in the developing cortex...
2017: PloS One
Nathaniel V Nucci
Calcium signaling serves as a nexus of many vital cellular processes. Of particular importance is the role the calcium signaling plays in the prevention of protein misfolding, and the S100 family of calcium-binding proteins is a key player in this pathway. While the S100 proteins carry out a range of roles, the interaction of S100A1 and the stress-inducible phosphoprotein 1 (STIP1) has been shown to be particularly important. A recent study by Maciejewski et al. in Biochemical Journal (Biochemical Journal (2017) 474, 1853-1866) revealed new insights into the nature of the S100A1-STIP1 interaction...
August 17, 2017: Biochemical Journal
Tiago F Jesus, João M Moreno, Tiago Repolho, Alekos Athanasiadis, Rui Rosa, Vera M F Almeida-Val, Maria M Coelho
Current knowledge on the biological responses of freshwater fish under projected scenarios of climate change remains limited. Here, we examine differences in the protein configuration of two endemic Iberian freshwater fish species, Squalius carolitertii and the critically endangered S. torgalensis that inhabit in the Atlantic-type northern and in the Mediterranean-type southwestern regions, respectively. We performed protein structure modeling of fourteen genes linked to protein folding, energy metabolism, circadian rhythms and immune responses...
2017: PloS One
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
August 3, 2017: Autophagy
Andrzej Maciejewski, Vania F Prado, Marco A M Prado, Wing-Yiu Choy
Stress-inducible phosphoprotein 1 (STIP1) is a cellular co-chaperone, which regulates heat-shock protein 70 (Hsp70) and Hsp90 activity during client protein folding. Members of the S100 family of dimeric calcium-binding proteins have been found to inhibit Hsp association with STIP1 through binding of STIP1 tetratricopeptide repeat (TPR) domains, possibly regulating the chaperone cycle. Here, we investigated the molecular basis of S100A1 binding to STIP1. We show that three S100A1 dimers associate with one molecule of STIP1 in a calcium-dependent manner...
May 16, 2017: Biochemical Journal
Jiang Wang, Hongbo You, Jun Qi, Caihong Yang, Ye Ren, Hao Cheng
Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis...
March 7, 2017: Oncotarget
Marta Brunetti, Antonio Agostini, Ben Davidson, Claes G Tropé, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
Juxtaposition of two different genes or gene parts due to chromosomal rearrangement is a well-known neoplasia-associated pathogenetic mechanism. The detection and characterization of such tumorigenic fusions is of great importance both research-wise, diagnostically because they may be specific for distinct tumor entities, and because they may serve as therapeutic targets for antioncogenic drugs that interact directly with the molecular changes responsible for neoplastic transformation.At present, more than 10,000 fusion transcripts have been reported in different types of neoplasia, with one tenth of them being identified in squamous cell carcinomas (SCC) of different locations...
March 7, 2017: Oncotarget
Yue Huang, Hao Li, Lei Wang, Xiaoxia Mao, Genxi Li
In this work, we have successfully designed a smart and flexible signal amplification method based on a newly synthesized hybrid nanocomposite with switchable enzyme activity for specific and sensitive protein detection. The smart hybrid nanocomposite synthesized here is initially loaded with quenched fluorophore and a unique aptamer-inhibited DNA polymerase. It then undergoes target protein-triggered release of the fluorophore and activation of the DNA polymerase, which can thereby promote multiple catalytic reactions and recycled use of the target protein, resulting in the generation of highly amplified signals...
October 4, 2016: ACS Applied Materials & Interfaces
Chia-Lung Tsai, Angel Chao, Shih-Ming Jung, Chi-Neu Tsai, Chiao-Yun Lin, Shun-Hua Chen, Shih-Che Sue, Tzu-Hao Wang, Hsin-Shih Wang, Chyong-Huey Lai
Overexpression of stress-induced phosphoprotein 1 (STIP1) - a co-chaperone of heat shock protein (HSP) 70/HSP90 - and activation of the JAK2-STAT3 pathway occur in several tumors. Combined treatment with a HSP90 inhibitor and a JAK2 inhibitor exert synergistic anti-cancer effects. Here, we show that STIP1 stabilizes JAK2 protein in ovarian and endometrial cancer cells. Knock-down of endogenous STIP1 decreased JAK2 and phospho-STAT3 protein levels. The N-terminal fragment of STIP1 interacts with the N-terminus of JAK2, whereas the C-terminal DP2 domain of STIP1 mediates the interaction with HSP90 and STAT3...
August 2, 2016: Oncotarget
Yu Guo, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by complex interactions between genes and the environment. The expression level of transcription factor regulatory factor X 1 (RFX1) is reduced in T cells from SLE patients. RFX1 can regulate epigenetic modifications of CD70 and CD11a and plays an important role in the development of SLE. However, the mechanisms that mediate reduction of RFX1 in SLE are unclear. Here, we demonstrate that RFX1 protein expression can be tightly regulated by polyubiquitination-mediated proteosomal degradation via STIP1 homology and U-box containing protein 1 (STUB1)...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Andrzej Maciejewski, Valeriy G Ostapchenko, Flavio H Beraldo, Vania F Prado, Marco A M Prado, Wing-Yiu Choy
Soluble oligomers of amyloid-beta peptide (AβO) transmit neurotoxic signals through the cellular prion protein (PrP(C)) in Alzheimer's disease (AD). Secreted stress-inducible phosphoprotein 1 (STIP1), an Hsp70 and Hsp90 cochaperone, inhibits AβO binding to PrP(C) and protects neurons from AβO-induced cell death. Here, we investigated the molecular interactions between AβO and STIP1 binding to PrP(C) and their effect on neuronal cell death. We showed that residues located in a short region of PrP (90-110) mediate AβO binding and we narrowed the major interaction in this site to amino acids 91-100...
July 15, 2016: Biochemical Journal
Marcin Gabryel, Marzena Skrzypczak-Zielinska, Marcin A Kucharski, Ryszard Slomski, Agnieszka Dobrowolska
Glucocorticosteroids (GCs) are used for many years as first-line drugs for the achievement of remission in exacerbations of inflammatory bowel disease (IBD). However, close to 20% of patients are resistant to GCs, and 40% of patients become dependent on GCs. The challenge of today's personalized medicine is the anticipation of the steroid therapy effects even before the initiation of treatment. As several studies show, individually variable response to GCs in population has a genetic background and may depend on gene variability encoding proteins involved in the function and metabolism of GCs...
2016: Scandinavian Journal of Gastroenterology
Khalequz Zaman, Victoria Sawczak, Atiya Zaidi, Maya Butler, Deric Bennett, Paulina Getsy, Maryam Zeinomar, Zivi Greenberg, Michael Forbes, Shagufta Rehman, Vinod Jyothikumar, Kim DeRonde, Abdus Sattar, Laura Smith, Deborah Corey, Adam Straub, Fei Sun, Lisa Palmer, Ammasi Periasamy, Scott Randell, Thomas J Kelley, Stephen J Lewis, Benjamin Gaston
S-nitrosoglutathione (GSNO) reductase regulates novel endogenous S-nitrosothiol signaling pathways, and mice deficient in GSNO reductase are protected from airways hyperreactivity. S-nitrosothiols are present in the airway, and patients with cystic fibrosis (CF) tend to have low S-nitrosothiol levels that may be attributed to upregulation of GSNO reductase activity. The present study demonstrates that 1) GSNO reductase activity is increased in the cystic fibrosis bronchial epithelial (CFBE41o(-)) cells expressing mutant F508del-cystic fibrosis transmembrane regulator (CFTR) compared with the wild-type CFBE41o(-) cells, 2) GSNO reductase expression level is increased in the primary human bronchial epithelial cells expressing mutant F508del-CFTR compared with the wild-type cells, 3) GSNO reductase colocalizes with cochaperone Hsp70/Hsp90 organizing protein (Hop; Stip1) in human airway epithelial cells, 4) GSNO reductase knockdown with siRNA increases the expression and maturation of CFTR and decreases Stip1 expression in human airway epithelial cells, 5) increased levels of GSNO reductase cause a decrease in maturation of CFTR, and 6) a GSNO reductase inhibitor effectively reverses the effects of GSNO reductase on CFTR maturation...
February 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Aline Ketefian, Michelle R Jones, Ronald M Krauss, Yii-Der I Chen, Richard S Legro, Ricardo Azziz, Mark O Goodarzi
OBJECTIVE: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). DESIGN: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters...
February 2016: Fertility and Sterility
Flavio H Beraldo, Anu Thomas, Benjamin Kolisnyk, Pedro H Hirata, Xavier De Jaeger, Amanda C Martyn, Jue Fan, Daniela F Goncalves, Matthew F Cowan, Talal Masood, Vilma R Martins, Robert Gros, Vania F Prado, Marco A M Prado
Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions...
November 2015: Disease Models & Mechanisms
Ana Paula Lappas Gimenez, Larissa Morato Luciani Richter, Mariana Campos Atherino, Breno Castello Branco Beirão, Celso Fávaro, Michele Dietrich Moura Costa, Silvio Marques Zanata, Bettina Malnic, Adriana Frohlich Mercadante
Prion diseases involve the conversion of the endogenous cellular prion protein, PrP(C), into a misfolded infectious isoform, PrP(Sc). Several functions have been attributed to PrP(C), and its role has also been investigated in the olfactory system. PrP(C) is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp(-/-) mice showed impaired behavior in olfactory tests. Given the high PrP(C) expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrP(C)-binding partners...
2015: Prion
Kazuhiro Tokuda, Yasuhiro Kuramitsu, Baron Byron, Takao Kitagawa, Nobuko Tokuda, Daiki Kobayashi, Megumi Nagayama, Norie Araki, Koh-Hei Sonoda, Kazuyuki Nakamura
Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage...
August 7, 2015: Biochemical and Biophysical Research Communications
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