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KMID : 1034820090050030230
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Molecular & Cellular Toxicology
2009 Volume.5 No. 3 p.230 ~ p.236
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Upregulation of Heme Oxygenase-1 as an Adaptive Mechanism against Acrolein in RAW 264.7 Macrophages
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Lee Nam-Ju
Lee Seung-Eun
Park Cheung-Seog
Ahn Hyun-Jong
Ahn Kyu-Jeong
Park Yong-Seek
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Abstract
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Acrolein, a known toxin in cigarette smoke, is the most abundant electrophilic α, β-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 , 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.
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KEYWORD
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Acrolein, HO-1, Macrophages, Adaptive response
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