title: 4-Hydroxynonenal induces an increase in expression of Receptor for Activating C Kinase 1 (RACK1) in Chinese hamster V79-4 lung cells.
abstract: 4-Hydroxy-trans-2-nonenal (HNE) is a cytotoxic α,β-unsaturated aldehyde implicated in the pathology of several diseases that have an oxidative stress mechanism, including atherosclerosis, diabetes, alcohol-induced liver disease, and neurodegenerative disorders. As the most toxic aldehydic product of lipid peroxidation, HNE is known to exert a range of biological effects in a concentration-dependent manner. In this study, the effect of HNE on the levels of proteins in V79-4 Chinese hamster lung cells was investigated using two-dimensional electrophoresis and mass spectrometry. The results revealed that the expression of 23 proteins was increased by at least 2-fold and the expression of 19 proteins was decreased by at least 2-fold after exposure to 10 μM HNE for 24 h. Decreased proteins included the metabolic enzyme phosphoglycerate kinase 1 (PGK1), levels of which were decreased by 47%. Levels of the apoptotic indicator Lamin C were decreased by 33%. In contrast, levels of the scaffolding protein Receptor for Activating C Kinase 1 (RACK1) were increased by 2-fold after treatment with 10 μM HNE for 24h, and this was confirmed using quantitative PCR of reverse-transcribed mRNA and Western blots. The role of RACK1 in mediating the induction of apoptosis in response to 10 μM HNE was confirmed using RACK1-specific siRNA. The results from this study provide new information on the mechanism of adaptive stress response to HNE and also identify potential new biomarkers of exposure to HNE.
authors: Department of Biopharmaceuticals, School of Pharmacy, China Medical University, Shenyang 110001, PR China; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom. Electronic address: lidan@mail.cmu.edu.cn.
authors: Dan
authors: D
authors: Li
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
authors: Elizabeth M
authors: EM
authors: Ellis
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003603:Cytotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D003603:Cytotoxins; D011506:Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C027576:4-hydroxy-2-nonenal
keywords: 2D electrophoresis; 4-Hydroxynonenal; Lamin C; Mass spectrometry; PGK1; RACK1