Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Aug 8;283(32):21837-41.
doi: 10.1074/jbc.R700019200. Epub 2008 Apr 29.

Oxidative stress and covalent modification of protein with bioactive aldehydes

Paul A Grimsrud  1 , Hongwei Xie, Timothy J Griffin, David A Bernlohr
Affiliations
Review

Oxidative stress and covalent modification of protein with bioactive aldehydes

Paul A Grimsrud et al. J Biol Chem. .

Abstract

The term "oxidative stress" links the production of reactive oxygen species to a variety of metabolic outcomes, including insulin resistance, immune dysfunction, and inflammation. Antioxidant defense systems down-regulated due to disease and/or aging result in oxidatively modified DNA, carbohydrates, proteins, and lipids. Increased production of hydroxyl radical leads to the formation of lipid hydroperoxides that produce a family of alpha,beta-unsaturated aldehydes. Such reactive aldehydes are subject to Michael addition reactions with the side chains of lysine, histidine, and cysteine residues, referred to as "protein carbonylation." Although not widely appreciated, reactive lipids can accumulate to high levels in cells, resulting in extensive protein modification leading to either loss or gain of function. The use of mass spectrometric methods to identify the site and extent of protein carbonylation on a proteome-wide scale has expanded our view of how oxidative stress can regulate cellular processes.

PubMed Disclaimer

Figures

FIGURE 1.
FIGURE 1.
Cellular fates of α,β-unsaturated aldehydes and carbonylated proteins. ROS stimulate peroxidation of polyunsaturated fatty acids (PUFA), an oxidative event that is reversible through reduction by peroxiredoxin (PRX) and glutathione peroxidase (GPX) enzymes. The lipid hydroperoxides (PUFA-OOH) generated are unstable and lead to a variety of reactive aldehydes. The lipid peroxidation products generated include the α,β-unsaturated aldehydes 4-HNE, 4-ONE, 4-hydroxy-(2E)-hexanal (4-HHE), (2E)-hexenal, crotonaldehyde, and acrolein as well as the dialdehydes glyoxal and malondialdehyde (MDA). GSTA4 catalyzes the conjugation of the highly reactive α,β-unsaturated aldehydes to glutathione, leading to their efflux from the cell by the glutathione conjugate transporter RLIP76. In addition, oxidation by aldehyde dehydrogenase or reduction by alcohol dehydrogenase, aldehyde reductase, or aldose reductase converts free aldehydes into less toxic molecules. The α,β-unsaturated aldehydes that escape cellular metabolism serve as electrophiles in the covalent modification of proteins via non-enzymatic Michael addition. The resulting aliphatic carbonyl adducts on cysteine, histidine, or lysine residues may alter the activity of protein targets or cause them to become degraded by the proteasome.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sayre, L. M., Smith, M. A., and Perry, G. (2001) Curr. Med. Chem. 8 721–738 - PubMed
    1. Schafer, F. Q., and Buettner, G. R. (2001) Free Radic. Biol. Med. 30 1191–1212 - PubMed
    1. Beatty, S., Koh, H., Phil, M., Henson, D., and Boulton, M. (2000) Surv. Ophthalmol. 45 115–134 - PubMed
    1. Tidball, J. G., and Wehling-Henricks, M. (2007) J. Appl. Physiol. 102 1677–1686 - PubMed
    1. Eriksson, J. W. (2007) FEBS Lett. 581 3734–3742 - PubMed

Publication types

LinkOut - more resources