title: N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) reflect accumulation of oxidative stress in diabetic patients.
abstract: While carboxymethylated proteins are considered to be advanced glycation end products (AGE), they can also be induced by reactive oxygen species (ROS) independently of the AGE-forming process. To clarify whether N-(carboxymethyl)valine residues in hemoglobin (CMV-Hb) were a useful marker of the accumulation of ROS in diabetes, we evaluated CMV-Hb formation in vitro and in vivo. For the in vitro studying, purified human hemoglobin was incubated with D-glucose or D-glucose and hydrogen peroxide. For the in vivo study, CMV-Hb was extracted from peripheral red blood cells in diabetic patients and compared with that from non-diabetic subjects. Furthermore, the effect of antioxidants was evaluated after 6 months in 15 diabetic patients showing very high CMV-Hb levels. In vitro CMV-Hb formation increased in a glucose concentration and time-dependent manner. Co-incubation with glucose and hydrogen peroxide synergistically increased CMV-Hb formation. The CMV-Hb level was higher in the diabetic group than the non-diabetic group, and CMV-Hb was correlated with the plasma total cholesterol and serum creatinine levels. The CMV-Hb level was decreased by antioxidant therapy, whereas HbA1c did not change. These results demonstrate that CMV-Hb may be a useful marker for accumulation of oxidative stress in diabetic patients.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shimada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Chie
authors.initials: C
authors.lastname: Ohmura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchino
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Tomiko
authors.initials: T
authors.lastname: Nakaniwa
authors.forename: Shinya
authors.initials: S
authors.lastname: Miwa
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood; D006454:Hemoglobins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D014633:Valine / Q000032:analysis
chemical_list: D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D014633:Valine; C120200:N-(carboxymethyl)valine