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Shruti Sharma, Kathryn E Bollinger, Sai Karthik Kodeboyina, Wenbo Zhi, Jordan Patton, Shan Bai, Blake Edwards, Lane Ulrich, David Bogorad, Ashok Sharma
Purpose: Primary open angle glaucoma (POAG) is the most prevalent form of glaucoma, accounting for approximately 90% of all cases. The aqueous humor (AH), a biological fluid in the anterior and posterior chambers of the eye, is involved in a multitude of functions including the maintenance of IOP and ocular homeostasis. This fluid is very close to the pathologic site and is also known to have a significant role in glaucoma pathogenesis. The purpose of this study was to identify proteomic alterations in AH from patients with POAG...
May 1, 2018: Investigative Ophthalmology & Visual Science
Xianyin Lai, Christopher B Umbricht, Kurt Fisher, Justin Bishop, Qiuying Shi, Shaoxiong Chen
Distinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Identification of biomarkers for improving diagnostic accuracy is important for clinical management. Meanwhile, it is critical to identify therapeutic target candidates for treatment of follicular carcinoma. Currently, no reliable diagnostic protein biomarkers and therapeutic targets are available. To explore novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to analyze control, follicular adenoma, and follicular carcinoma using formalin-fixed, paraffin-embedded tissue samples...
August 23, 2017: Journal of Proteomics
Gergely Kacso, Dora Ravasz, Judit Doczi, Beáta Németh, Ory Madgar, Ann Saada, Polina Ilin, Chaya Miller, Elsebet Ostergaard, Iordan Iordanov, Daniel Adams, Zsuzsanna Vargedo, Masatake Araki, Kimi Araki, Mai Nakahara, Haruka Ito, Aniko Gál, Mária J Molnár, Zsolt Nagy, Attila Patocs, Vera Adam-Vizi, Christos Chinopoulos
Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and a substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with or without methylmalonyl aciduria, in addition to resulting in mitochondrial DNA depletion. We generated mice lacking either one Sucla2 or Suclg2 allele. Sucla2 heterozygote mice exhibited tissue- and age-dependent decreases in Sucla2 expression associated with decreases in ATP-forming activity, but rebound increases in cardiac Suclg2 expression and GTP-forming activity...
October 15, 2016: Biochemical Journal
Taraka R Donti, Ruchi Masand, Daryl A Scott, William J Craigen, Brett H Graham
Deficiency of the TCA cycle enzyme Succinyl-CoA Synthetase/Ligase (SCS), due to pathogenic variants in subunits encoded by SUCLG1 and SUCLA2, causes mitochondrial encephalomyopathy, methylmalonic acidemia, and mitochondrial DNA (mtDNA) depletion. In this study, we report an 11year old patient who presented with truncal ataxia, chorea, hypotonia, bilateral sensorineural hearing loss and preserved cognition. Whole exome sequencing identified a heterozygous known pathogenic variant and a heterozygous novel missense variant of uncertain clinical significance (VUS) in SUCLG1...
September 2016: Molecular Genetics and Metabolism
Zhong-Wei Xu, Xi Chen, Xiao-Han Jin, Xiang-Yan Meng, Xin Zhou, Feng-Xu Fan, Shi-Yun Mao, Yue Wang, Wen-Cheng Zhang, Na-Na Shan, Yu-Ming Li, Rui-Cheng Xu
Hypoxic status alters the energy metabolism and induces cell injury in cardiomyocytes, and it further triggers the occurrence and development of cardiovascular diseases. Our previous studies have shown that salidroside (SAL) exhibits anti-hypoxic activity. However, the mechanisms remain obscure. In the present study, we successfully screened 92 different expression proteins in CoCl2-induced hypoxic conditions, 106 different expression proteins in the SAL-mediated anti-hypoxic group were compared with the hypoxic group using quantitative proteomics strategy, respectively...
January 1, 2016: Journal of Proteomics
Xiulai Chen, Pan Zhu, Liming Liu
Microbial fumarate production from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. Here, we report a modular engineering approach that systematically removed metabolic pathway bottlenecks and led to significant titer improvements in a multi-gene fumarate metabolic pathway. On the basis of central pathway architecture, yeast fumarate biosynthesis was re-cast into three modules: reduction module, oxidation module, and byproduct module. We targeted reduction module and oxidation module to the cytoplasm and the mitochondria, respectively...
January 2016: Metabolic Engineering
Aleksandra Konieczna, Aneta Szczepańska, Karolina Sawiuk, Grzegorz Węgrzyn, Robert Łyżeń
BACKGROUND: Previously published reports indicated that some enzymes of the central carbon metabolism (CCM), particularly those involved in glycolysis and the tricarboxylic acid cycle, may contribute to regulation of DNA replication. However, vast majority of such works was performed with the use of cancer cells, in the light of carcinogenesis. On the other hand, recent experiments conducted on bacterial models provided evidence for the direct genetic link between CCM and DNA replication...
2015: BMC Cell Biology
Y-L Huang, Q Fu, L Yang, J-L Guan, H Pan, F-M Chen, K-L Lu, M Zhang
This study was undertaken to investigate differences in protein expression between high- and low-motility sperm of swamp buffalo. The research used two-dimensional gel electrophoresis (2DE) coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS) to analyse the different proteins. The results showed 18 different expression protein spots between high- and low-motility buffalo sperm; eight of these proteins were up-regulated in low-motility sperm, five were down-regulated, one deleted and four proteins specifically expressed...
June 2015: Reproduction in Domestic Animals, Zuchthygiene
Xiulai Chen, Xiaoxiang Dong, Yuancai Wang, Zihao Zhao, Liming Liu
Microbial fumarate production from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. Here, mitochondrial engineering was used to construct the oxidative pathway for fumarate production starting from the TCA cycle intermediate α-ketoglutarate in Candida glabrata. Accordingly, α-ketoglutarate dehydrogenase complex (KGD), succinyl-CoA synthetase (SUCLG), and succinate dehydrogenase (SDH) were selected to be manipulated for strengthening the oxidative pathway, and the engineered strain T...
September 2015: Metabolic Engineering
Arpád Dobolyi, Attila G Bagó, Aniko Gál, Mária J Molnár, Miklós Palkovits, Vera Adam-Vizi, Christos Chinopoulos
We have recently shown that the ATP-forming SUCLA2 subunit of succinyl-CoA ligase, an enzyme of the citric acid cycle, is exclusively expressed in neurons of the human cerebral cortex; GFAP- and S100-positive astroglial cells did not exhibit immunohistoreactivity or in situ hybridization reactivity for either SUCLA2 or the GTP-forming SUCLG2. However, Western blotting of post mortem samples revealed a minor SUCLG2 immunoreactivity. In the present work we sought to identify the cell type(s) harboring SUCLG2 in paraformaldehyde-fixed, free-floating surgical human cortical tissue samples...
April 2015: Journal of Bioenergetics and Biomembranes
Alfredo Ramirez, Wiesje M van der Flier, Christine Herold, David Ramonet, Stefanie Heilmann, Piotr Lewczuk, Julius Popp, André Lacour, Dmitriy Drichel, Eva Louwersheimer, Markus P Kummer, Carlos Cruchaga, Per Hoffmann, Charlotte Teunissen, Henne Holstege, Johannes Kornhuber, Oliver Peters, Adam C Naj, Vincent Chouraki, Céline Bellenguez, Amy Gerrish, Reiner Heun, Lutz Frölich, Michael Hüll, Lara Buscemi, Stefan Herms, Heike Kölsch, Philip Scheltens, Monique M Breteler, Eckart Rüther, Jens Wiltfang, Alison Goate, Frank Jessen, Wolfgang Maier, Michael T Heneka, Tim Becker, Markus M Nöthen
Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers...
December 15, 2014: Human Molecular Genetics
Arpád Dobolyi, Elsebet Ostergaard, Attila G Bagó, Tamás Dóczi, Miklós Palkovits, Aniko Gál, Mária J Molnár, Vera Adam-Vizi, Christos Chinopoulos
SUCLA2 encodes the ATP-forming β subunit (A-SUCL-β) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye...
January 2015: Brain Structure & Function
Yalda Afshar, Julie Hastings, Damian Roqueiro, Jae-Wook Jeong, Linda C Giudice, Asgerally T Fazleabas
Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons (n = 4) by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected during the midsecretory phase (Days 9-11 postovulation) at 1, 3, 6-7, 10-12, and 15-16 mo after disease induction and compared with tissue from disease-free baboons...
February 2013: Biology of Reproduction
Osamu Sakamoto, Toshihiro Ohura, Kei Murayama, Akira Ohtake, Hiroko Harashima, Daiki Abukawa, Junji Takeyama, Kazuhiro Haginoya, Shigeaki Miyabayashi, Shigeo Kure
BACKGROUND: Succinyl-coenzyme A ligase (SUCL) is a mitochondrial enzyme that catalyses the reversible conversion of succinyl-coenzyme A to succinate. SUCL consists of an α subunit, encoded by SUCLG1, and a β subunit, encoded by either SUCLA2 or SUCLG2. Recently, mutations in SUCLG1 or SUCLA2 have been identified in patients with infantile lactic acidosis showing elevated urinary excretion of methylmalonate, mitochondrial respiratory chain (MRC) deficiency, and mitochondrial DNA depletion...
December 2011: Pediatrics International: Official Journal of the Japan Pediatric Society
Chaya Miller, Liya Wang, Elsebet Ostergaard, Phyllis Dan, Ann Saada
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is a result of mutations in the β subunit of the ADP-dependent isoform of the Krebs cycle succinyl-CoA synthase (SCS). The mechanism of tissue specificity and mtDNA depletion is elusive but complementation by the GDP-dependent isoform encoded by SUCLG2, and the association with mitochondrial nucleoside diphosphate kinase (NDPK), is a plausible link. We have investigated this relationship by studying SUCLA2 deficient fibroblasts derived from patients and detected normal mtDNA content and normal NDPK activity...
May 2011: Biochimica et Biophysica Acta
Su Jin Park, Seong Hwan Kim, Han Seok Choi, Yumie Rhee, Sung-Kil Lim
Fibroblast growth factor 2 (FGF2), the potent bone anabolic agent, regulates the bone development, as well as the growth, remodeling and healing of the fracture. The intracellular signaling of FGF2 leads to activation of genes involved in cell proliferation, migration, differentiation and survival. However, little is known about FGF2-regulated proteins in the osteoblasts. Therefore, in this study, protein profiling in FGF2-treated MC3T3-E1 preosteoblast cells was evaluated using proteomic technologies. Six proteins including asparaginyl-tRNA synthetase (NARS), eukaryotic translation termination factor 1 (ETF1), GDP-forming succinyl-CoA synthetase (SUCLG2), heat shock protein 84 (HSP 84), sorting nexin 9 (SNX9) and alpha glucosidase 2alpha neutral subunit (GANAB) were increased more than 3-fold after the FGF2 treatment...
November 2009: Bone
E Ostergaard
Succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP. It is a mitochondrial matrix enzyme and at least the ADP-forming enzyme is part of the Krebs cycle. The substrate specificity is determined by the beta subunit of succinate-CoA ligase, which is encoded by either SUCLA2 or SUCLG2. In patients with severe hypotonia, deafness and Leigh-like syndrome, mutations have been found in SUCLA2. Mutations have also been reported in SUCLG1, which encodes the alpha subunit found in both enzymes, in patients with severe infantile acidosis and lactic aciduria...
April 2008: Journal of Inherited Metabolic Disease
Dominique Hazard, Laurence Liaubet, Magali Sancristobal, Pierre Mormède
BACKGROUND: Variability in hypothalamic-pituitary-adrenal (HPA) axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS) and Large White (LW) pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation...
2008: BMC Genomics
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