TY - JOUR
T1 - 4-Hydroxynonenal induces an increase in expression of receptor for activating C Kinase 1 (RACK1) in Chinese hamster V79-4 lung cells
AU - Li, Dan
AU - Ellis, Elizabeth M
PY - 2014/4/25
Y1 - 2014/4/25
N2 - 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.
AB - 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.
KW - 4-hydroxynonenal
KW - increase in expression
KW - receptor
KW - c kinase 1
KW - rack1
KW - hanster
KW - v79-4
KW - lung cells
UR - http://www.scopus.com/inward/record.url?scp=84896713777&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2014.01.020
DO - 10.1016/j.cbi.2014.01.020
M3 - Article
C2 - 24525193
SN - 0009-2797
VL - 213
SP - 13
EP - 20
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -
