Protein Carbonylation, Cellular Dysfunction, and Disease Progression

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2006 Jun 27

PMID 16796807

Citations 256

Authors

Isabella Dalle-Donne

Giancarlo Aldini

Marina Carini

Roberto Colombo

Ranieri Rossi

Aldo Milzani

Affiliations

Soon will be listed here.

Abstract

Carbonylation of proteins is an irreversible oxidative damage, often leading to a loss of protein function, which is considered a widespread indicator of severe oxidative damage and disease-derived protein dysfunction. Whereas moderately carbonylated proteins are degraded by the proteasomal system, heavily carbonylated proteins tend to form high-molecular-weight aggregates that are resistant to degradation and accumulate as damaged or unfolded proteins. Such aggregates of carbonylated proteins can inhibit proteasome activity. Alarge number of neurodegenerative diseases are directly associated with the accumulation of proteolysis-resistant aggregates of carbonylated proteins in tissues. Identification of specific carbonylated protein(s) functionally impaired and development of selective carbonyl blockers should lead to the definitive assessment of the causative, correlative or consequential role of protein carbonylation in disease onset and/or progression, possibly providing new therapeutic approaches.

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References

Keller J, Schmitt F, Scheff S, Ding Q, Chen Q, Butterfield D . Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology. 2005; 64(7):1152-6. DOI: 10.1212/01.WNL.0000156156.13641.BA. View

Lee M, Hyun D, Jenner P, Halliwell B . Effect of proteasome inhibition on cellular oxidative damage, antioxidant defences and nitric oxide production. J Neurochem. 2001; 78(1):32-41. DOI: 10.1046/j.1471-4159.2001.00416.x. View

Beal M . Oxidatively modified proteins in aging and disease. Free Radic Biol Med. 2002; 32(9):797-803. DOI: 10.1016/s0891-5849(02)00780-3. View

Nystrom T . Role of oxidative carbonylation in protein quality control and senescence. EMBO J. 2005; 24(7):1311-7. PMC: 1142534. DOI: 10.1038/sj.emboj.7600599. View

Yan L, Levine R, Sohal R . Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci U S A. 1997; 94(21):11168-72. PMC: 23404. DOI: 10.1073/pnas.94.21.11168. View

Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley P . Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes. 2003; 52(8):2110-20. DOI: 10.2337/diabetes.52.8.2110. View

Ishii T, Sakurai T, Usami H, Uchida K . Oxidative modification of proteasome: identification of an oxidation-sensitive subunit in 26 S proteasome. Biochemistry. 2005; 44(42):13893-901. DOI: 10.1021/bi051336u. View

Merker K, Grune T . Proteolysis of oxidised proteins and cellular senescence. Exp Gerontol. 2000; 35(6-7):779-86. DOI: 10.1016/s0531-5565(00)00140-6. View

Wataya T, Nunomura A, Smith M, Siedlak S, Harris P, Shimohama S . High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal. J Biol Chem. 2001; 277(7):4644-8. DOI: 10.1074/jbc.M110913200. View

10.

Aksenov M, Aksenova M, Butterfield D, Geddes J, Markesbery W . Protein oxidation in the brain in Alzheimer's disease. Neuroscience. 2001; 103(2):373-83. DOI: 10.1016/s0306-4522(00)00580-7. View

11.

Pedersen W, Fu W, Keller J, Markesbery W, Appel S, Smith R . Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann Neurol. 1998; 44(5):819-24. DOI: 10.1002/ana.410440518. View

12.

Fortun J, Li J, Go J, Fenstermaker A, Fletcher B, Notterpek L . Impaired proteasome activity and accumulation of ubiquitinated substrates in a hereditary neuropathy model. J Neurochem. 2005; 92(6):1531-41. DOI: 10.1111/j.1471-4159.2004.02987.x. View

13.

Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman E, Mizuno Y . Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A. 1996; 93(7):2696-701. PMC: 39693. DOI: 10.1073/pnas.93.7.2696. View

14.

Wilson M . Clusterin is a secreted mammalian chaperone. Trends Biochem Sci. 2000; 25(3):95-8. DOI: 10.1016/s0968-0004(99)01534-0. View

15.

Dawson T, Dawson V . Molecular pathways of neurodegeneration in Parkinson's disease. Science. 2003; 302(5646):819-22. DOI: 10.1126/science.1087753. View

16.

Yan L, Levine R, Sohal R . Effects of aging and hyperoxia on oxidative damage to cytochrome c in the housefly, Musca domestica. Free Radic Biol Med. 2000; 29(1):90-7. DOI: 10.1016/s0891-5849(00)00323-3. View

17.

Powell S, Wang P, Divald A, Teichberg S, Haridas V, McCloskey T . Aggregates of oxidized proteins (lipofuscin) induce apoptosis through proteasome inhibition and dysregulation of proapoptotic proteins. Free Radic Biol Med. 2005; 38(8):1093-101. DOI: 10.1016/j.freeradbiomed.2005.01.003. View

18.

Miyata T, van Ypersele de Strihou C, Ueda Y, Ichimori K, Inagi R, Onogi H . Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol. 2002; 13(10):2478-87. DOI: 10.1097/01.asn.0000032418.67267.f2. View

19.

Baynes J . Role of oxidative stress in development of complications in diabetes. Diabetes. 1991; 40(4):405-12. DOI: 10.2337/diab.40.4.405. View

20.

Refsgaard H, Tsai L, Stadtman E . Modifications of proteins by polyunsaturated fatty acid peroxidation products. Proc Natl Acad Sci U S A. 2000; 97(2):611-6. PMC: 15378. DOI: 10.1073/pnas.97.2.611. View