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Title: Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats.

Authors: Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

Published In Toxicol Appl Pharmacol, (2014 Aug 15)

Abstract: The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress.

PubMed ID: 24832492 Exiting the NIEHS site

MeSH Terms: Aldehydes/antagonists & inhibitors; Aldehydes/metabolism*; Animals; Antibodies, Blocking/pharmacology; Blotting, Western; Brain/drug effects; Brain/enzymology; Brain/metabolism*; Enzyme Inhibitors/pharmacology; Glutathione Transferase/antagonists & inhibitors; Glutathione Transferase/metabolism; Hepatocytes/drug effects; Hepatocytes/metabolism; Kinetics; Liver/drug effects; Liver/enzymology; Liver/metabolism*; Lung/drug effects; Lung/enzymology; Lung/metabolism*; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Long-Evans; Species Specificity; Subcellular Fractions/enzymology; Subcellular Fractions/metabolism

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