Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Upregulation of Heme Oxygenase-1 as an Adaptive Mechanism against Acrolein in RAW 264.7 Macrophages

  • Lee, Nam-Ju (Department of Microbiology (BK21) and MRC for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University) ;
  • Lee, Seung-Eun (Department of Microbiology (BK21) and MRC for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University) ;
  • Park, Cheung-Seog (Department of Microbiology (BK21) and MRC for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University) ;
  • Ahn, Hyun-Jong (Department of Microbiology (BK21) and MRC for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University) ;
  • Ahn, Kyu-Jeung (Endocrinology and Metabolism Center, Kyung Hee East-West Neo Medical Center) ;
  • Park, Yong-Seek (Department of Microbiology (BK21) and MRC for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University)
  • Published : 2009.09.30
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Abstract

Acrolein, a known toxin in cigarette smoke, is the most abundant electrophilic $\alpha$, $\beta$-unsaturated aldehyde to which humans are exposed in a variety of environmental pollutants, and is also product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status plays a major role in the pathogenesis of various diseases such as diabetes, Alzheimer's and atherosclerosis. The findings reported here show that low concentrations of acrolein induce heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophages. HO-1 induction by acrolein and signal pathways was measured using reverse transcription-polymerase chain reaction, Western blot and immunofluorescence staining analyses. Inhibition of extracellular signal-regulated kinase activity significantly attenuated the induction of HO-1 protein by acrolein, while suppression of Jun N-terminal kinase and p38 activity did not affect induction of HO-1 expression. Moreover, rottlerin, an inhibitor of protein kinase $\delta$, suppressed the upregulation of HO-1 protein production, possibly involving the interaction of NF-E2-related factor 2 (Nrf2), which has a key role as a HO-1 transcription factor. Acrolein elevated the nuclear translocation of Nrf2 in nuclear extraction. The results suggest that RAW 264.7 may protect against acrolein-mediated cellular damage via the upregulation of HO-1, which is an adaptive response to oxidative stress.

Keywords

References

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