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Advanced Glycation End Products in Histone H1 In Vivo
Author(s) -
Cervantes Laurean Daniel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.863.6
Subject(s) - glycation , chemistry , histone , lysine , biochemistry , in vivo , oxidative stress , dna damage , amino acid , dna , biology , genetics , receptor
Oxidative stress leads to protein and DNA damage, which is involved in aging and cancer. The role of protein damage in the alteration of genomic integrity is not well defined. Protein damage by glycation, non‐enzymatic reaction of hydroxy aldehydes with amino groups in proteins, correlates with complications of diabetes, actinic elastosis and the aging process. Glycation is a reversible, non‐enzymatic reaction between reducing sugars and amino groups of proteins that undergo rearrangements to stable ketoamines, which lead to the formation of advanced glycation end products (AGEs) such as fluorescent (argpyrimidine) and non‐fluorescent ( Nε − carboxymethyllysine, CML) protein adducts and protein crosslinks. We look for in vivo AGEs adduct formation in nuclear proteins, specifically histone H1, using CML and argpyrimidine as biomarkers. Histone H1 isolated from calf thymus was examined due to its relevance in genomic integrity homeostasis. It was determined the presence of CML and argpyrimidine in histone H1, purified by HPLC, using antibodies against CML and argpyrimidine. Furthermore, CML was quantified using a sensitive chemical method. MS/MS mass spectroscopy analysis of histone H1 revealed the presence of two lysine residues being modified with CML adducts. Our results indicate that glycation of important nuclear targets accumulates in histone H1 under in vivo conditions and this should open the field into exploring AGE protein damage ant its role in the pathophysiology of aging and diabetes.