Detoxication of the environmental pollutant acrolein by a rat liver aldo-keto reductase.
Acrolein is a highly reactive hazardous air pollutant of human health concern, particularly as it is a component of cigarette smoke. It can be metabolized by enzymes including the aldo-keto reductase (AKR) family of enzymes. AKR7A1 is a member of the AKR7 sub-family and can catalyse the reduction of toxic aldehydes, including alpha-unsaturated carbonyl compounds, to alcohols [Biochem. J. 312 (1995) 535]. In this study, the role of AKR7A1 in protecting against acrolein toxicity has been assessed by stably-expressing a cDNA encoding AKR7A1 in Chinese hamster V79 cells. Cells expressing AKR7A1 showed over 2-fold increased resistance to acrolein compared to V79 cells alone, as measured by 3-[4,4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays. IC50 increased from 45 microM in control V79-pCI-neo cells to 125microM for V79-AKR7A1 cells. Cells expressing AKR7A1 were also found to be less susceptible to DNA damage, showing a decrease in mutation rate in the presence of acrolein as measured by hypoxanthine guanine phosphoribosyl transferase (HGPRT) mutagenicity assays. The mutation rate for acrolein-exposed control cells was 20-fold higher than for acrolein-exposed AKR7A1-expressing cells. These results indicate that AKR7A1 has the potential to protect against acrolein-induced damage in vivo.
Gardner
Rachel
R
Departments of Bioscience and Pharmaceutical Sciences, Royal College, University of Strathclyde, 204, George Street, Glasgow G1 1XW, Scotland, UK.
Kazi
Shubana
S
Ellis
Elizabeth M
EM
D000171:Acrolein / Q000378:metabolism* / Q000633:toxicity; D000393:Air Pollutants / Q000378:metabolism* / Q000633:toxicity; D000449:Aldehyde Reductase / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005347:Fibroblasts
D000393:Air Pollutants; D018076:DNA, Complementary; D000171:Acrolein; C442302:AKR7A1; D000449:Aldehyde Reductase