Logo of biochemjBJ Latest papers and much more!
Biochem J. 2000 Nov 1; 351(Pt 3): 769–777.
PMCID: PMC1221418

Histone carbonylation in vivo and in vitro.


Non-enzymic damage to nuclear proteins has potentially severe consequences for the maintenance of genomic integrity. Introduction of carbonyl groups into histones in vivo and in vitro was assessed by Western blot immunoassay and reductive incorporation of tritium from radiolabelled NaBH(4) (sodium borohydride). Histone H1 extracted from bovine thymus, liver and spleen was found to contain significantly elevated amounts of protein-bound carbonyl groups as compared with core histones. The carbonyl content of nuclear proteins of rat pheochromocytoma cells (PC12 cells) was not greatly increased following oxidative stress induced by H(2)O(2), but was significantly increased following alkylating stress induced by N-methyl-N'-nitro-N-nitrosoguanidine or by combined oxidative and alkylating stress. Free ADP-ribose, a reducing sugar generated in the nucleus in proportion to DNA strand breaks, was shown to be a potent histone H1 carbonylating agent in isolated PC12 cell nuclei. Studies of the mechanism of histone H1 modification by ADP-ribose indicate that carbonylation involves formation of a stable acyclic ketoamine. Our results demonstrate preferential histone H1 carbonylation in vivo, with potentially important consequences for chromatin structure and function.

Full Text

The Full Text of this article is available as a PDF (220K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995;46:223–234. [PubMed]
  • Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997 Aug 15;272(33):20313–20316. [PubMed]
  • Lindner H, Sarg B, Hoertnagl B, Helliger W. The microheterogeneity of the mammalian H1(0) histone. Evidence for an age-dependent deamidation. J Biol Chem. 1998 May 22;273(21):13324–13330. [PubMed]
  • Luxford C, Morin B, Dean RT, Davies MJ. Histone H1- and other protein- and amino acid-hydroperoxides can give rise to free radicals which oxidize DNA. Biochem J. 1999 Nov 15;344(Pt 1):125–134. [PMC free article] [PubMed]
  • Stadtman ER. Role of oxidized amino acids in protein breakdown and stability. Methods Enzymol. 1995;258:379–393. [PubMed]
  • Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J. 1997 May 15;324(Pt 1):1–18. [PMC free article] [PubMed]
  • Liggins J, Furth AJ. Role of protein-bound carbonyl groups in the formation of advanced glycation endproducts. Biochim Biophys Acta. 1997 Aug 22;1361(2):123–130. [PubMed]
  • Fu S, Fu MX, Baynes JW, Thorpe SR, Dean RT. Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs): amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins. Biochem J. 1998 Feb 15;330(Pt 1):233–239. [PMC free article] [PubMed]
  • Pleshakova OV, Kutsyi MP, Sukharev SA, Sadovnikov VB, Gaziev AI. Study of protein carbonyls in subcellular fractions isolated from liver and spleen of old and gamma-irradiated rats. Mech Ageing Dev. 1998 Jun 1;103(1):45–55. [PubMed]
  • Ullrich O, Reinheckel T, Sitte N, Hass R, Grune T, Davies KJ. Poly-ADP ribose polymerase activates nuclear proteasome to degrade oxidatively damaged histones. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6223–6228. [PMC free article] [PubMed]
  • Gugliucci A, Bendayan M. Histones from diabetic rats contain increased levels of advanced glycation end products. Biochem Biophys Res Commun. 1995 Jul 6;212(1):56–62. [PubMed]
  • Medina L, Haltiwanger RS. Calf thymus high mobility group proteins are nonenzymatically glycated but not significantly glycosylated. Glycobiology. 1998 Feb;8(2):191–198. [PubMed]
  • Takata K, Horiuchi S, Araki N, Shiga M, Saitoh M, Morino Y. Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins. J Biol Chem. 1988 Oct 15;263(29):14819–14825. [PubMed]
  • Johns EW. Studies on histones. 7. Preparative methods for histone fractions from calf thymus. Biochem J. 1964 Jul;92(1):55–59. [PMC free article] [PubMed]
  • Bonnieu A, Rech J, Jeanteur P, Fort P. Requirements for c-fos mRNA down regulation in growth stimulated murine cells. Oncogene. 1989 Jul;4(7):881–888. [PubMed]
  • Ruiz-Carrillo A, Jorcano JL. An octamer of core histones in solution: central role of the H3-H4 tetramer in the self-assembly. Biochemistry. 1979 Mar 6;18(5):760–768. [PubMed]
  • Chao CC, Ma YS, Stadtman ER. Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2969–2974. [PMC free article] [PubMed]
  • Cervantes-Laurean D, Jacobson EL, Jacobson MK. Glycation and glycoxidation of histones by ADP-ribose. J Biol Chem. 1996 May 3;271(18):10461–10469. [PubMed]
  • Shacter E, Williams JA, Lim M, Levine RL. Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay. Free Radic Biol Med. 1994 Nov;17(5):429–437. [PubMed]
  • Lenz AG, Costabel U, Shaltiel S, Levine RL. Determination of carbonyl groups in oxidatively modified proteins by reduction with tritiated sodium borohydride. Anal Biochem. 1989 Mar;177(2):419–425. [PubMed]
  • Jacobson MK, Levi V, Juarez-Salinas H, Barton RA, Jacobson EL. Effect of carcinogenic N-alkyl-N-nitroso compounds on nicotinamide adenine dinucleotide metabolism. Cancer Res. 1980 Jun;40(6):1797–1802. [PubMed]
  • Jacobson EL, Antol KM, Juarez-Salinas H, Jacobson MK. Poly(ADP-ribose) metabolism in ultraviolet irradiated human fibroblasts. J Biol Chem. 1983 Jan 10;258(1):103–107. [PubMed]
  • Jacobson EL, Cervantes-Laurean D, Jacobson MK. ADP-ribose in glycation and glycoxidation reactions. Adv Exp Med Biol. 1997;419:371–379. [PubMed]
  • Shearman MS, Ragan CI, Iversen LL. Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid-mediated cell death. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1470–1474. [PMC free article] [PubMed]
  • Elgawish A, Glomb M, Friedlander M, Monnier VM. Involvement of hydrogen peroxide in collagen cross-linking by high glucose in vitro and in vivo. J Biol Chem. 1996 May 31;271(22):12964–12971. [PubMed]
  • Edelstein D, Brownlee M. Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine. Diabetes. 1992 Jan;41(1):26–29. [PubMed]
  • Cervantes-Laurean D, Minter DE, Jacobson EL, Jacobson MK. Protein glycation by ADP-ribose: studies of model conjugates. Biochemistry. 1993 Feb 16;32(6):1528–1534. [PubMed]
  • Acharya AS, Manning JM. Amadori rearrangement of glyceraldehyde-hemoglobin Schiff base adducts. A new procedure for the determination of ketoamine adducts in proteins. J Biol Chem. 1980 Aug 10;255(15):7218–7224. [PubMed]
  • Stadtman ER. Protein oxidation and aging. Science. 1992 Aug 28;257(5074):1220–1224. [PubMed]
  • Levine RL, Williams JA, Stadtman ER, Shacter E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 1994;233:346–357. [PubMed]
  • Yan LJ, Levine RL, Sohal RS. Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11168–11172. [PMC free article] [PubMed]
  • Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER. Age-related changes in oxidized proteins. J Biol Chem. 1987 Apr 25;262(12):5488–5491. [PubMed]
  • Commerford SL, Carsten AL, Cronkite EP. Histone turnover within nonproliferating cells. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1163–1165. [PMC free article] [PubMed]
  • Ullrich O, Sitte N, Sommerburg O, Sandig V, Davies KJ, Grune T. Influence of DNA binding on the degradation of oxidized histones by the 20S proteasome. Arch Biochem Biophys. 1999 Feb 15;362(2):211–216. [PubMed]
  • Kreimeyer A, Wielckens K, Adamietz P, Hilz H. DNA repair-associated ADP-ribosylation in vivo. Modification of histone H1 differs from that of the principal acceptor proteins. J Biol Chem. 1984 Jan 25;259(2):890–896. [PubMed]
  • Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000 Jan 6;403(6765):41–45. [PubMed]
  • Enright HU, Miller WJ, Hebbel RP. Nucleosomal histone protein protects DNA from iron-mediated damage. Nucleic Acids Res. 1992 Jul 11;20(13):3341–3346. [PMC free article] [PubMed]
  • Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA., Jr The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11140–11145. [PMC free article] [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...