title: High glucose-induced proteome alterations in hepatocytes and its possible relevance to diabetic liver disease.
abstract: Hyperglycemia can cause several abnormalities in liver cells, including diabetic liver disease. Previous research has shown that high blood glucose levels can damage liver cells through glycoxidation. However, the detailed molecular mechanisms underlying the effects of high blood glucose on the development of diabetic liver disease have yet to be elucidated. In this study, we cultured a liver cell line (Chang liver cell) in mannitol-balanced 5.5 mM, 25 mM and 100 mM d-glucose media and evaluated protein expression and redox regulation. We identified 141 proteins that showed significant changes in protein expression and 29 proteins that showed significant changes in thiol reactivity, in response to high glucose concentration. Several proteins involved in transcription-control, signal transduction, redox regulation and cytoskeleton regulation showed significant changes in expression, whereas proteins involved in protein folding and gene regulation displayed changes in thiol reactivity. Further analyses of clinical plasma specimens confirmed that the proteins AKAP8L, galectin-3, PGK 1, syntenin-1, Abin 2, aldose reductase, CD63, GRP-78, GST-pi, RXR-gamma, TPI and vimentin showed type 2 diabetic liver disease-dependent alterations. In summary, in this study we used a comprehensive hepatocyte-based proteomic approach to identify changes in protein expression and to identify redox-associated diabetic liver disease markers induced by high glucose concentration. Some of the identified proteins were validated with clinical samples and are presented as potential targets for the prognosis and diagnosis of diabetic liver disease.
authors.affiliation: Institute of Bioinformatics and Structural Biology & Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Chen
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Chou
authors.forename: You-Hsuan
authors.initials: YH
authors.lastname: Chen
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Chan
mesh_terms: D002460:Cell Line; D048909:Diabetes Complications; D005947:Glucose / Q000008:administration & dosage* / Q000009:adverse effects; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology*; D010084:Oxidation-Reduction; D020543:Proteome / Q000187:drug effects; D040901:Proteomics; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D020543:Proteome; D005947:Glucose
keywords: 1-DE; 2-DE; 2D-DIGE; 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate); Ab; CCB; CHAPS; DIGE; DTT; FCS; Glucose proteomics; Liver cells; MALDI-TOF MS; NP-40; Nonidet P-40; Redox-proteomics; TFA; antibody; colloidal coomassie blue; ddH(2)O; differential gel electrophoresis; dithiothreitol; double deionized water; fetal calf serum; matrix assisted laser desorption ionization-time of flight mass spectrometry; one-dimensional gel electrophoresis; trifluoroacetic acid; two-dimensional gel electrophoresis