Formation of a protein-bound pyrazinium free radical cation during glycation of histone H1

Georg T Wondrak, Sridhar Varadarajan, D. Allan Butterfield, Myron K. Jacobson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glycation, the nonenzymatic reaction between protein amino groups and reducing sugars, induces protein damage that has been linked to several pathological conditions, especially diabetes, and general aging. Here we describe the direct identification of a protein-bound free radical formed during early glycation of histone H1 in vitro. Earlier EPR analysis of thermal browning reactions between free amino acids and reducing sugars has implicated the sugar fragmentation product glycolaldehyde in the generation of a 1,4-disubstituted pyrazinium free radical cation. In order to evaluate the potential formation of this radical in vivo, the early glycation of BSA, lysozyme, and histone H1 by several sugars (D-glucose, D-ribose, ADP-ribose, glycolaldehyde) under conditions of physiological pH and temperature was examined by EPR. The pyrazinium free radical cation was identified on histone H1 glycated by glycolaldehyde (g = 2.00539, a(N) = 8.01 [2N], a(H) = 5.26 [4H], a(H) = 2.72 [4H]), or ADP-ribose. Reaction of glycolaldehyde with poly- L-lysine produced an identical signal, whereas reaction with BSA or lysozyme produced only a minor unresolved singlet signal. In the absence of oxygen the signal was stable over several days. Our results raise the possibility that pyrazinium radicals may form during glycation of histone H1 in vivo. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)557-567
Number of pages11
JournalFree Radical Biology and Medicine
Volume29
Issue number6
DOIs
StatePublished - Sep 15 2000
Externally publishedYes

Fingerprint

Sugars
Histones
Free Radicals
Cations
Adenosine Diphosphate Ribose
Muramidase
Paramagnetic resonance
Proteins
Maillard Reaction
Ribose
Medical problems
Lysine
Hot Temperature
Aging of materials
Oxygen
Amino Acids
Glucose
Temperature
glycolaldehyde

Keywords

  • ADP-ribose
  • Electron paramagnetic resonance
  • Free radicals
  • Glutathione
  • Glycation
  • Glycolaldehyde
  • Histone H1
  • Pyrazinium free radical

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

Cite this

Formation of a protein-bound pyrazinium free radical cation during glycation of histone H1. / Wondrak, Georg T; Varadarajan, Sridhar; Butterfield, D. Allan; Jacobson, Myron K.

In: Free Radical Biology and Medicine, Vol. 29, No. 6, 15.09.2000, p. 557-567.

Research output: Contribution to journalArticle

Wondrak, Georg T ; Varadarajan, Sridhar ; Butterfield, D. Allan ; Jacobson, Myron K. / Formation of a protein-bound pyrazinium free radical cation during glycation of histone H1. In: Free Radical Biology and Medicine. 2000 ; Vol. 29, No. 6. pp. 557-567.
@article{954f76f37e15487a91ff1a7906107722,
title = "Formation of a protein-bound pyrazinium free radical cation during glycation of histone H1",
abstract = "Glycation, the nonenzymatic reaction between protein amino groups and reducing sugars, induces protein damage that has been linked to several pathological conditions, especially diabetes, and general aging. Here we describe the direct identification of a protein-bound free radical formed during early glycation of histone H1 in vitro. Earlier EPR analysis of thermal browning reactions between free amino acids and reducing sugars has implicated the sugar fragmentation product glycolaldehyde in the generation of a 1,4-disubstituted pyrazinium free radical cation. In order to evaluate the potential formation of this radical in vivo, the early glycation of BSA, lysozyme, and histone H1 by several sugars (D-glucose, D-ribose, ADP-ribose, glycolaldehyde) under conditions of physiological pH and temperature was examined by EPR. The pyrazinium free radical cation was identified on histone H1 glycated by glycolaldehyde (g = 2.00539, a(N) = 8.01 [2N], a(H) = 5.26 [4H], a(H) = 2.72 [4H]), or ADP-ribose. Reaction of glycolaldehyde with poly- L-lysine produced an identical signal, whereas reaction with BSA or lysozyme produced only a minor unresolved singlet signal. In the absence of oxygen the signal was stable over several days. Our results raise the possibility that pyrazinium radicals may form during glycation of histone H1 in vivo. (C) 2000 Elsevier Science Inc.",
keywords = "ADP-ribose, Electron paramagnetic resonance, Free radicals, Glutathione, Glycation, Glycolaldehyde, Histone H1, Pyrazinium free radical",
author = "Wondrak, {Georg T} and Sridhar Varadarajan and Butterfield, {D. Allan} and Jacobson, {Myron K.}",
year = "2000",
month = "9",
day = "15",
doi = "10.1016/S0891-5849(00)00406-8",
language = "English (US)",
volume = "29",
pages = "557--567",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Formation of a protein-bound pyrazinium free radical cation during glycation of histone H1

AU - Wondrak, Georg T

AU - Varadarajan, Sridhar

AU - Butterfield, D. Allan

AU - Jacobson, Myron K.

PY - 2000/9/15

Y1 - 2000/9/15

N2 - Glycation, the nonenzymatic reaction between protein amino groups and reducing sugars, induces protein damage that has been linked to several pathological conditions, especially diabetes, and general aging. Here we describe the direct identification of a protein-bound free radical formed during early glycation of histone H1 in vitro. Earlier EPR analysis of thermal browning reactions between free amino acids and reducing sugars has implicated the sugar fragmentation product glycolaldehyde in the generation of a 1,4-disubstituted pyrazinium free radical cation. In order to evaluate the potential formation of this radical in vivo, the early glycation of BSA, lysozyme, and histone H1 by several sugars (D-glucose, D-ribose, ADP-ribose, glycolaldehyde) under conditions of physiological pH and temperature was examined by EPR. The pyrazinium free radical cation was identified on histone H1 glycated by glycolaldehyde (g = 2.00539, a(N) = 8.01 [2N], a(H) = 5.26 [4H], a(H) = 2.72 [4H]), or ADP-ribose. Reaction of glycolaldehyde with poly- L-lysine produced an identical signal, whereas reaction with BSA or lysozyme produced only a minor unresolved singlet signal. In the absence of oxygen the signal was stable over several days. Our results raise the possibility that pyrazinium radicals may form during glycation of histone H1 in vivo. (C) 2000 Elsevier Science Inc.

AB - Glycation, the nonenzymatic reaction between protein amino groups and reducing sugars, induces protein damage that has been linked to several pathological conditions, especially diabetes, and general aging. Here we describe the direct identification of a protein-bound free radical formed during early glycation of histone H1 in vitro. Earlier EPR analysis of thermal browning reactions between free amino acids and reducing sugars has implicated the sugar fragmentation product glycolaldehyde in the generation of a 1,4-disubstituted pyrazinium free radical cation. In order to evaluate the potential formation of this radical in vivo, the early glycation of BSA, lysozyme, and histone H1 by several sugars (D-glucose, D-ribose, ADP-ribose, glycolaldehyde) under conditions of physiological pH and temperature was examined by EPR. The pyrazinium free radical cation was identified on histone H1 glycated by glycolaldehyde (g = 2.00539, a(N) = 8.01 [2N], a(H) = 5.26 [4H], a(H) = 2.72 [4H]), or ADP-ribose. Reaction of glycolaldehyde with poly- L-lysine produced an identical signal, whereas reaction with BSA or lysozyme produced only a minor unresolved singlet signal. In the absence of oxygen the signal was stable over several days. Our results raise the possibility that pyrazinium radicals may form during glycation of histone H1 in vivo. (C) 2000 Elsevier Science Inc.

KW - ADP-ribose

KW - Electron paramagnetic resonance

KW - Free radicals

KW - Glutathione

KW - Glycation

KW - Glycolaldehyde

KW - Histone H1

KW - Pyrazinium free radical

UR - http://www.scopus.com/inward/record.url?scp=0034665331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034665331&partnerID=8YFLogxK

U2 - 10.1016/S0891-5849(00)00406-8

DO - 10.1016/S0891-5849(00)00406-8

M3 - Article

C2 - 11025199

AN - SCOPUS:0034665331

VL - 29

SP - 557

EP - 567

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 6

ER -