NYMC Faculty Publications

Differential Metabolism of 4-Hydroxynonenal in Liver, Lung and Brain of Mice and Rats

Author Type(s)

Faculty

DOI

10.1016/j.taap.2014.04.026

Journal Title

Toxicology and Applied Pharmacology

First Page

43

Last Page

52

Document Type

Article

Publication Date

8-15-2014

Department

Pharmacology

Keywords

Aldehydes, Animals, Antibodies, Blocking, Blotting, Western, Brain, Enzyme Inhibitors, Glutathione Transferase, Hepatocytes, Kinetics, Liver, Lung, Male, Mice, Mice, Inbred C57BL, Rats, Rats, Long-Evans, Species Specificity, Subcellular Fractions

Disciplines

Medicine and Health Sciences

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.

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