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Hezhen Li, Bingxi Lei, Wei Xiang, Hai Wang, Wenfeng Feng, Yawei Liu, Songtao Qi
AIM: The U251 and U87 cell lines are commonly used as experimental models of glioblastoma multiforme. However, these cells exhibit significant differences in their proliferation, invasion, and migration Material and Methods: The present study was to compare the protein expression profiles of the U251 and U87 cell lines in order to provide a molecular basis for the observed phenotypic differences. Isobaric tags for relative and absolute quantitation (iTRAQ) and gene ontology (GO) analyses were performed to detect differentially expressed proteins and to predict protein functions, respectively Results: 244 proteins were highly expressed, while 263 proteins exhibited lower levels of expression, in the U251 cells compared to the U87 cells...
August 23, 2016: Turkish Neurosurgery
Yongliang Shang, Hongna Wang, Pengfei Jia, Haichao Zhao, Chao Liu, Weixiao Liu, Zhenhua Song, Zhiliang Xu, Lin Yang, Yanfang Wang, Wei Li
Spermiogenesis is a complex and highly ordered spermatid differentiation process that requires reorganization of cellular structures. We have previously found that Atg7 is required for acrosome biogenesis. Here, we show that autophagy regulates the round and elongating spermatids. Specifically, we found that Atg7 is required for spermatozoa flagella biogenesis and cytoplasm removal during spermiogenesis. Spermatozoa motility of atg7-null mice dropped significantly with some extra-cytoplasm retained on the mature sperm head...
September 2016: Autophagy
Genki Hayashi, Gino Cortopassi
There is no current approved therapy for the ultimately lethal neuro- and cardio-degenerative disease Friedreich's ataxia (FA). Finding minimally-invasive molecular biomarkers of disease progression and drug effect could support smaller, shorter clinical trials. Since we and others have noted a deficient oxidative stress response in FA, we investigated the expression of 84 genes involved in oxidative stress, signaling, and protection in control and FA lymphoblasts ranging from 460 to 1122 GAA repeats. Several antioxidant genes responded in a dose-dependent manner to frataxin expression at the mRNA and protein levels, which is inversely correlated with disease progression and severity...
2016: PloS One
Prachi Gupta, Shankar Suman, Manisha Mishra, Sanjay Mishra, Nidhi Srivastava, Vijay Kumar, Pradhyumna Kumar Singh, Yogeshwer Shukla
PURPOSE: Breast cancer (BC) is the most common invasive cancer in women worldwide. Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have a great potential for the development of diagnostic biomarkers in cancer. This study was performed to identify AAbs and cognate TAAs that may improve detection of this deadly disease. EXPERIMENTAL DESIGN: Serological proteome analysis of plasma samples of BC patients (N = 30) and healthy controls (N = 30) was performed to identify TAAs...
May 2016: Proteomics. Clinical Applications
Chao Liu, Hongna Wang, Yongliang Shang, Weixiao Liu, Zhenhua Song, Haichao Zhao, Lina Wang, Pengfei Jia, Fengyi Gao, Zhiliang Xu, Lin Yang, Fei Gao, Wei Li
The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads...
May 3, 2016: Autophagy
Doo-Sik Kong, Jinkuk Kim, In-Hee Lee, Sung Tae Kim, Ho Jun Seol, Jung-Il Lee, Woong-Yang Park, Gyuha Ryu, Zichen Wang, Avi Ma'ayan, Do-Hyun Nam
We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image...
March 8, 2016: Oncotarget
Hai-Ning Chen, Kefei Yuan, Na Xie, Kui Wang, Zhao Huang, Yan Chen, Qianhui Dou, Min Wu, Edouard C Nice, Zong-Guang Zhou, Canhua Huang
Metastasis is a major cause of death in patients with colorectal cancer, and increasing evidence supports the contribution of the epithelial-mesenchymal transition (EMT) to cancer progression. The dissociation of the E-cadherin/β-catenin adhesion complex represents a key step in EMT and promotes cancer invasion and metastasis, but the upstream signaling pathways regulating this interaction are poorly understood. Here, we show that PDLIM1, a member of the PDZ and LIM protein family, was downregulated in highly metastatic colorectal cancer cells and liver metastases from colorectal cancer patients...
March 1, 2016: Cancer Research
Rumiko Ono, Tsuneyasu Kaisho, Takashi Tanaka
Understanding the regulatory mechanisms for the NF-κB transcription factor is key to control inflammation. IκBα maintains NF-κB in an inactive form in the cytoplasm of unstimulated cells, whereas nuclear NF-κB in activated cells is degraded by PDLIM2, a nuclear ubiquitin E3 ligase that belongs to a LIM protein family. How NF-κB activation is negatively controlled, however, is not completely understood. Here we show that PDLIM1, another member of LIM proteins, negatively regulates NF-κB-mediated signaling in the cytoplasm...
2015: Scientific Reports
B Y Ahn, R F G Saldanha-Gama, J J Rahn, X Hao, J Zhang, N-H Dang, M Alshehri, S M Robbins, D L Senger
The invasive nature of glioblastoma renders them incurable by current therapeutic interventions. Using a novel invasive human glioma model, we previously identified the neurotrophin receptor p75(NTR) (aka CD271) as a mediator of glioma invasion. Herein, we provide evidence that preventing phosphorylation of p75(NTR) on S303 by pharmacological inhibition of PKA, or by a mutational strategy (S303G), cripples p75(NTR)-mediated glioma invasion resulting in serine phosphorylation within the C-terminal PDZ-binding motif (SPV) of p75(NTR)...
March 17, 2016: Oncogene
Z Liu, Y Zhan, Y Tu, K Chen, Z Liu, C Wu
Increased CLP36 expression has been found to be closely associated with breast cancer progression. However, whether and how it contributes to malignant behavior of breast cancer cells were not known. We show here that CLP36 is critical for promoting breast cancer cell migration and invasion in vitro and metastasis in vivo, whereas it is dispensable for breast cell proliferation and anchorage-independent growth in vitro and tumor growth in vivo. CLP36 interacted with both α-actinin-1 and -4 in breast cancer cells...
March 5, 2015: Oncogene
Ross Clark, Amanda Nosie, Teresa Walker, Jennifer A Faralli, Mark S Filla, Gregory Barrett-Wilt, Donna M Peters
Changes in the actin cytoskeleton, especially the formation of cross-linked actin networks (CLANs) are thought to contribute to the increased intraocular pressure observed in primary open-angle and steroid-induced glaucoma. To better understand the effects of glucocorticoids, we employed a shotgun method to analyze global changes in the cytoskeleton and integrin signaling pathways following dexamethasone (DEX) treatment of human trabecular meshwork (HTM) cells. RNA and cell lysates were obtained from HTM cells incubated with or without DEX...
January 2013: Molecular & Cellular Proteomics: MCP
Małgorzata Sikorska, Artur Krężel, Jacek Otlewski
An individual LIM domain has approximately 55 amino acids with 8 highly conserved residues responsible for binding of two Zn(2+) into two distinct zinc finger motifs. We examined LIM domain stability of PDLIM1 protein (known also as Elfin protein), its C-terminally extended constructs as well as separate zinc fingers, and several full domain mutants in terms of Zn(2+) affinity and domain stability. Thermal denaturation, mass spectrometry, limited proteolysis, protein oxidation and circular dichroism techniques were used to determine a set of thermodynamic stability parameters...
October 2012: Journal of Inorganic Biochemistry
Kristen M Naegle, Forest M White, Douglas A Lauffenburger, Michael B Yaffe
Cell signaling networks propagate information from extracellular cues via dynamic modulation of protein-protein interactions in a context-dependent manner. Networks based on receptor tyrosine kinases (RTKs), for example, phosphorylate intracellular proteins in response to extracellular ligands, resulting in dynamic protein-protein interactions that drive phenotypic changes. Most commonly used methods for discovering these protein-protein interactions, however, are optimized for detecting stable, longer-lived complexes, rather than the type of transient interactions that are essential components of dynamic signaling networks such as those mediated by RTKs...
October 2012: Molecular BioSystems
Umamaheswari Ramachandran, Arulmani Manavalan, Husvinee Sundaramurthi, Siu Kwan Sze, Zhi Wei Feng, Jiang-Miao Hu, Klaus Heese
Tianma (Rhizoma gastrodiae) is the dried rhizome of the plant Gastrodia elata Blume (Orchidaceae family). As a medicinal herb in traditional Chinese medicine (TCM) its functions are to control convulsions, pain, headache, dizziness, vertigo, seizure, epilepsy and others. In addition, tianma is frequently used for the treatment of neurodegenerative disorders though the mechanism of action is widely unknown. Accordingly, this study was designed to examine the effects of tianma on the proteome metabolism in differentiated human neuronal SH-SY5Y cells to explore its specific effects on neuronal signaling pathways...
June 2012: Neurochemistry International
Ke-Sheng Wang, Xuefeng Liu, Qunyuan Zhang, Nagesh Aragam, Yue Pan
BACKGROUND: Previous studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder(ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample. METHODS: Family-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios...
January 2012: Journal of Psychiatry & Neuroscience: JPN
Parveen Sharma, Thiruchelvi Shathasivam, Vladimir Ignatchenko, Thomas Kislinger, Anthony O Gramolini
INTRODUCTION: Four and a half LIM domains protein 1 (FHL1) is the most widely expressed member of the FHL family of proteins, consisting of four and a half highly conserved LIM domains. A multifunctional and integral role for FHL1 has been implicated in muscle development, structural maintenance, and signaling. To date, 27 FHL1 mutations have been identified that result in at least six different X-linked myopathies, with patients often presenting with cardiovascular complications. Since proteins assemble into dynamic complexes within the cell, FHL1 likely mediates its biological functions in conjunction with other proteins...
April 2011: Molecular BioSystems
Bi-Hua Cheng, Yunlong Liu, Xiaoling Xuei, Chung-Ping Liao, Debao Lu, Mark E Lasbury, Pamela J Durant, Chao-Hung Lee
BACKGROUND: Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts. To understand how Pneumocystis inactivates alveolar macrophages, Affymetrix GeneChip RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected and Pneumocystis carinii-infected Sprague-Dawley rats...
2010: BMC Microbiology
Jonathan M Elkins, Carina Gileadi, Leela Shrestha, Claire Phillips, Jing Wang, João R C Muniz, Declan A Doyle
PDZ domains most commonly bind the C-terminus of their protein targets. Typically the C-terminal four residues of the protein target are considered as the binding motif, particularly the C-terminal residue (P0) and third-last residue (P-2) that form the major contacts with the PDZ domain's "binding groove". We solved crystal structures of seven human PDZ domains, including five of the seven PDLIM family members. The structures of GRASP, PDLIM2, PDLIM5, and PDLIM7 show a binding mode with only the C-terminal P0 residue bound in the binding groove...
April 2010: Protein Science: a Publication of the Protein Society
Ilenia Bertipaglia, Natalie Bourg, Isabelle Richard, Anna-Karin Pahlman, Liselotte Andersson, Peter James, Ernesto Carafoli
Limb-girdle muscular dystrophy type 2A is an autosomal recessive disorder generated by inactivating mutations in the gene coding for the muscle specific protease calpain-3. It is mainly expressed in skeletal muscle as a monomeric multidomain protein characterized by three unique insertion sequences (NS, IS1, IS2). It is unstable, and undergoes very rapid autolysis in solution, therefore, its heterologous expression and purification have been difficult. So far, calpain-3 substrates have been only identified in vitro and with indirect approaches...
November 2009: Cell Calcium
Koji Ohno, Hiroshi Kato, Shinji Funahashi, Tomohiko Hasegawa, Kohji Sato
CLP36, one of the alpha-Actinin Associated LIM Protein (ALP)/Enigma family proteins, has a wide tissue distribution, but little is known about its expression and role in the nervous system. We show here that CLP36 is expressed in sensory ganglia but not in the CNS of adult rats. In primary dorsal root ganglion (DRG) neurons, CLP36 is distributed in the soma and neurites with enrichment in the growth cones. CLP36 forms a complex with alpha-actinin and is localized to actin cytoskeleton. To examine the role of CLP36 in neuronal cells, we transfected PC12 cells with a series of CLP36 deletion mutants and found that over-expression of CLP36 PDZ domain affects neurite outgrowth...
November 2009: Journal of Neurochemistry
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