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J Huang, J Yang, Y Lei, H Gao, T Wei, L Luo, F Zhang, H Chen, Q Zeng, L Guo
Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia especially in China. We previously identified that ANCCA/PRO2000 as an important proliferation-associated protein predicted poor prognosis of patients with HCC. However, the molecular mechanisms of ANCCA/PRO2000 leading to hepatocarcinogenesis and progression are still obscure. In the present study, we found that ANCCA/PRO2000 overexpression in HCC specimens correlated with aggressive tumor behavior and poor survival. Furthermore, ANCCA/PRO2000 exerts strong oncogenic function in HCC and promotes cell proliferation by regulating E2F2 expression, a critical cell cycle regulator...
2016: Oncogenesis
Chiung-Hung Hsu, Chia-Wei Hsu, Chuen Hsueh, Chih-Liang Wang, Yi-Cheng Wu, Chih-Ching Wu, Chin-Ching Liu, Jau-Song Yu, Yu-Sun Chang, Chia-Jung Yu
Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1...
July 2016: Molecular & Cellular Proteomics: MCP
So-Young Seol, Chul Kim, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Purpose: Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreduction 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer. Materials and Methods: For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 56 independent stage III gastric cancer patients...
February 26, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Junjie Xie, Yi Zhu, Hao Chen, Minmin Shi, Jiangning Gu, Jiaqiang Zhang, Baiyong Shen, Xiaxing Deng, Xi Zhan, Chenghong Peng
Solid pseudopapillary tumor of the pancreas (SPTP) is a class of low-grade malignant tumors that carry a favorable prognosis after surgery. Our group has reported that dysfunctions in the endoplasmic reticulum (ER) protein processing pathway may play a role in tumor development. However, alterations of this pathway in other pancreatic tumors had not been well investigated. In this study, we collected 35 SPTP and pancreatic neuroendocrine tumor (PNET) specimens and described the clinicopathological features of them...
January 2016: Medicine (Baltimore)
Yunyan Gu, Pengfei Li, Fuduan Peng, Mengmeng Zhang, Yuanyuan Zhang, Haihai Liang, Wenyuan Zhao, Lishuang Qi, Hongwei Wang, Chenguang Wang, Zheng Guo
Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset...
March 2016: Molecular Carcinogenesis
Qiang-Hong Pu, Jun-Lin He, Ming-Jun Wu, Jia-Jia Li, Zhu Yang, Ying-Xiong Wang, Chao Yu
AIMS: Neurodegenerative diseases are the leading cause of morbidity and mortality worldwide. Several studies have shown that tetramethylpyrazine (TMP) is an effective therapy for neurodegenerative diseases and that it acts by inhibiting the activation of microglial cells in response to inflammatory stimuli. However, the molecular mechanisms underlying the action of TMP remain unknown. MAIN METHODS: Proteomic analysis was used to generate novel insights into the mechanism by which TMP inhibits microglial activation, and western blotting was used to validate candidate proteins...
January 15, 2015: Life Sciences
Bing-Li Wu, Guo-Qing Lv, Hai-Ying Zou, Ze-Peng Du, Jian-Yi Wu, Pi-Xian Zhang, Li-Yan Xu, En-Min Li
LOXL2 (lysyl oxidase-like 2), an enzyme that catalyzes oxidative deamination of lysine residue, is upregulated in esophageal squamous cell carcinoma (ESCC). A LOXL2 splice variant LOXL2-e13 and its wild type were overexpressed in ESCC cells followed by microarray analyses. In this study, we explored the potential role and molecular mechanism of LOXL2-e13 based on known protein-protein interactions (PPIs), following microarray analysis of KYSE150 ESCC cells overexpressing a LOXL2 splice variant, denoted by LOXL2-e13, or its wild-type counterpart...
2014: TheScientificWorldJournal
Gisela Campos, Wolfgang Schmidt-Heck, Ahmed Ghallab, Katharina Rochlitz, Larissa Pütter, Danilo B Medinas, Claudio Hetz, Agata Widera, Cristina Cadenas, Brigitte Begher-Tibbe, Raymond Reif, Georgia Günther, Agapios Sachinidis, Jan G Hengstler, Patricio Godoy
Since xenobiotics enter the organism via the liver, hepatocytes must cope with numerous perturbations, including modifications of proteins leading to endoplasmic reticulum stress (ER-stress). This triggers a signaling pathway termed unfolded protein response (UPR) that aims to restore homeostasis or to eliminate disturbed hepatocytes by apoptosis. In the present study, we used the well-established CCl4 hepatotoxicity model in mice to address the questions whether CCl4 induces ER-stress and, if so, whether the well-known ER-stress effector CHOP is responsible for CCl4-induced apoptosis...
June 2014: Archives of Toxicology
M Ballester, A Castelló, R Peiró, M J Argente, M A Santacreu, J M Folch
Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating of two lines of rabbits divergently selected for uterine capacity were generated to identify differentially expressed genes. A total of 438 singletons and 126 contigs were obtained by cluster assembly and sequence alignment of 704 expressed sequence tags (ESTs), of which 54% showed homology to known proteins of the non-redundant NCBI databases. Differential screening by dot blot validated 71 ESTs, of which 47 showed similarity to known genes...
June 2013: Animal Genetics
Qinqiang Long, Xiaoyue Zhu, Yanling Wu, Bin Feng, Dan Jin, Jing Huang, Ting Lei, Li Gan, Zaiqing Yang
Disulfide bond formation is a pivotal step in the maturation and release of secretory proteins that is controlled by specific endoplasmic reticulum (ER) resident enzymes. An important element in this process is Ero (ER oxidoreduction), a glycosylated flavoenzyme tightly associated with oxidative protein folding that lacks the known ER retention motifs. ER resident protein 44kDa (ERp44) is an ER resident protein that mediates ERo1 localization in ER and also prevents the secretion of unassembled cargo proteins with unpaired cysteine...
September 1, 2011: General and Comparative Endocrinology
Phillip H Gallo, Latha Satish, Sandra Johnson, Sandeep Kathju
BACKGROUND: Adult mammalian tissues heal injury to the skin with formation of scar; this process quickly seals an injured area, however, excessive scar formation can become a source of persistent pathology, interfering with multiple vital functions. In contrast, mammalian fetal tissue can heal without scar formation. We previously sought to model scarless healing in a rabbit fetal skin wound and identified gene products differentially expressed during fetal wound healing through PCR suppression subtractive hybridization (PCR SSH)...
2011: BMC Research Notes
Cynthia Khoo, Juxiang Yang, Gautam Rajpal, You Wang, Jiangying Liu, Peter Arvan, Doris A Stoffers
Hyperglycemia increases insulin flux through the endoplasmic reticulum (ER) of pancreatic β-cells, and the unfolded protein response pathway is required to enhance insulin processing. Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion. Here we find that PDX1 is a direct transcriptional regulator of ER oxidoreductin-1-like β (Ero1lβ), which maintains the oxidative environment of the ER to facilitate disulfide bond formation...
July 2011: Endocrinology
King-Tung Chin, Guoxin Kang, Jiaxiang Qu, Lawrence B Gardner, William A Coetzee, Ester Zito, Glenn I Fishman, David Ron
Two related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in the mammalian endoplasmic reticulum (ER). Redox changes in cysteine residues on intralumenal loops of calcium release and reuptake channels have been implicated in altered calcium release and reuptake. These findings led us to hypothesize that altered ERO1 activity may affect cardiac functions that are dependent on intracellular calcium flux. We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β...
August 2011: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Chaya Mohan, Gyun Min Lee
To enhance specific antibody (Ab) productivity (q(Ab)) of recombinant Chinese hamster ovary (rCHO) cells, post-translational limitations in the endoplasmic reticulum during antibody production should be relieved. Previously, we reported that overexpression of protein disulfide isomerase (PDI), which catalyzes disulfide bond exchanges and assists in protein folding of newly synthesized proteins, enhanced q(Ab) of rCHO cells by about 27% (Mohan et al., 2007, Biotechnol Bioeng 98:611-615) . Since the rate limiting step in disulfide bond formation is found to be the regeneration of oxidized PDI, the oxidation state of PDI, as well as the amount of PDI, might be important...
October 1, 2010: Biotechnology and Bioengineering
Ester Zito, King-Tung Chin, Jaime Blais, Heather P Harding, David Ron
Mammals have two genes encoding homologues of the endoplasmic reticulum (ER) disulfide oxidase ERO1 (ER oxidoreductin 1). ERO1-beta is greatly enriched in the endocrine pancreas. We report in this study that homozygosity for a disrupting allele of Ero1lb selectively compromises oxidative folding of proinsulin and promotes glucose intolerance in mutant mice. Surprisingly, concomitant disruption of Ero1l, encoding the other ERO1 isoform, ERO1-alpha, does not exacerbate the ERO1-beta deficiency phenotype. Although immunoglobulin-producing cells normally express both isoforms of ERO1, disulfide bond formation and immunoglobulin secretion proceed at nearly normal pace in the double mutant...
March 22, 2010: Journal of Cell Biology
Balázs Enyedi, Péter Várnai, Miklós Geiszt
Formation of intra- and intermolecular disulfide bonds is an essential step in the synthesis of secretory proteins. In eukaryotic cells, this process occurs in the endoplasmic reticulum (ER) and requires an oxidative environment with the action of several chaperones and folding catalysts. During protein folding, Ero1p oxidizes protein disulfide isomerase (PDI), which then directly catalyzes the formation of disulfide bonds in folding proteins. Recent cell-free studies suggest that the terminal electron acceptor in the pathway is molecular oxygen, with the resulting formation of hydrogen peroxide (H(2)O(2))...
September 15, 2010: Antioxidants & Redox Signaling
An-Chi Tien, Akhila Rajan, Karen L Schulze, Hyung Don Ryoo, Melih Acar, Hermann Steller, Hugo J Bellen
Notch-mediated cell-cell communication regulates numerous developmental processes and cell fate decisions. Through a mosaic genetic screen in Drosophila melanogaster, we identified a role in Notch signaling for a conserved thiol oxidase, endoplasmic reticulum (ER) oxidoreductin 1-like (Ero1L). Although Ero1L is reported to play a widespread role in protein folding in yeast, in flies Ero1L mutant clones show specific defects in lateral inhibition and inductive signaling, two characteristic processes regulated by Notch signaling...
September 22, 2008: Journal of Cell Biology
Yugo Miyata, Atsunori Fukuhara, Morihiro Matsuda, Ryutaro Komuro, Iichiro Shimomura
Adipocyte secretes bioactive proteins called adipocytokines, and biosynthesis of secretory proteins requires molecular chaperones and folding enzymes in endoplasmic reticulum (ER). ER chaperones are known to be induced by unfolded protein response (UPR) and growth factors, however, it has not been determined how ER chaperones expression is regulated in adipocytes. Here we show that insulin treatment induced GRP78 and ERO1L mRNA levels in 3T3-L1 adipocytes. Insulin also upregulated CHOP mRNA levels, but did not induce phosphorylation of eIF2alpha...
January 25, 2008: Biochemical and Biophysical Research Communications
Malin Gustavsson, Carina Mallard, Susan J Vannucci, Mary Ann Wilson, Michael V Johnston, Henrik Hagberg
We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature in the immature brain and thereby affects the cerebral blood flow (CBF) during a subsequent hypoxic-ischemic (HI) insult. On postnatal day 6 rats were exposed to hypoxia (36 degrees C, 8.0% O2) or normoxia for 3 h. Unilateral HI (unilateral carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was measured with the 14C-iodoantipyrine technique (at the end of HI) or with laser Doppler flowmetry (Perimed PF5001) before and during HI...
May 2007: Journal of Cerebral Blood Flow and Metabolism
Hideki Endoh, Shuta Tomida, Yasushi Yatabe, Hiroyuki Konishi, Hirotaka Osada, Kohei Tajima, Hiroyuki Kuwano, Takashi Takahashi, Tetsuya Mitsudomi
PURPOSE: Recently, several expression-profiling experiments have shown that adenocarcinoma can be classified into subgroups that also reflect patient survival. In this study, we examined the expression patterns of 44 genes selected by these studies to test whether their expression patterns were relevant to prognosis in our cohort as well, and to create a prognostic model applicable to clinical practice. PATIENTS AND METHODS: Expression levels were determined in 85 adenocarcinoma patients by quantitative reverse transcriptase polymerase chain reaction...
March 1, 2004: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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