4-Hydroxynonenal induces an increase in expression of receptor for activating C Kinase 1 (RACK1) in Chinese hamster V79-4 lung cells

Dan Li, Elizabeth M Ellis

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 10μM HNE for 24h. 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 10μM 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 10μM 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.

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalChemico-Biological Interactions
Volume213
Early online date10 Feb 2014
DOIs
Publication statusPublished - 25 Apr 2014

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Keywords

  • 4-hydroxynonenal
  • increase in expression
  • receptor
  • c kinase 1
  • rack1
  • hanster
  • v79-4
  • lung cells

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