1998 Fiscal Year Final Research Report Summary
Role of oxidative DNA damage in the pathogenesis of diabetic complications
| Project/Area Number |
09671019
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
SUZUKI Susumu Tohoku University, 3rd Dep Int Med, research associate, 医学部・附属病院, 助手 (70216399)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HINOKIO Yoshinori Tohoku University, 3rd Dep Int Med, research associate, 医学部・附属病院, 助手 (10282071)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | Oxidative stress / 8-oxo-2'-deoxyguanosine / mitochondrial DNA / diabetic nephropathy / diabetic retinopathy / アポトーシス / DNA損傷 |
|---|
| Research Abstract |
Augmented oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine(dG) to 8-oxo, 2'-deoxyguanosine (8-oxodG) in DNA.To investigate the possible. contribution of oxidative DNA damage to the pathogenesis of diabetic complicfttions, we measured the 8-oxodGcontents in the urine and the blood mononuclear cells of type 2 diabetic patients.
The contents of 8-oxodG in the urine and the mononuclear cells of the type 2 diabetic patients were much higher than those of the control subjects. Urinary excretion of 8-oxodG was significantly correlated with the 8-oxodG content in the mononuclear cells (R=0.855, p<0.0001). The 8-oxodGcontents in the urine (R=0.783, p<0.0001) and mononuclear cells (R=0.796, p.<0.0001) were correlated with the hemoglobin A1c level. Urinary 8-oxodG excretion and the 8-oxodG content in the mononuclear cells were augmented in proportion to the severity of diabetic nephropathy as well as retinopathy. These data provide evidence that augmented oxidative DNA damage in diabetes is linked to diabetic complications.
This is the first report showing that the increase in 8-oxodG is proportional to the severity of diabetic complications. Oxidative DNA damage is speculated to contribute to the pathogenesis of diabetic complications. 8-oxodG in urine and mononuclear cells is a useful marker to evaluate oxidative DNA damage in diabetic patients.
|
-
-
-
-
-
-
-
-
-
[Publications] S.Suzuki, Y.Hinokio, K.Komatu, M.Ohtomo, M.Onoda, S.Hirai, M.Hirai, A.Hirai, M.Chiba, S.Kasuga, H.Akai and T.Toyota: "Oxidative DNA damage and its relationship to diabetic complications." Diabetes Res Clin Pract. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] N.Matsuura, S.Suzuki, M.Hirai, Y.Yokota, K.Kazahari, M.Kazahari, T.Toyota, A.Okuno, S.Harada, N.Fukushima, A.Koike, Y.Itoh and T.Hotsubo.: "Mitochondrial gene mutations associated with childhood diabe-tes mellitus in Japanese." J Pediatric Endcrinol Metab. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] M.Hirai, S.Suzuki, M.Onoda, Y.Hinokio, A.Hirai, M.Ohtomo, M.Chiba, S.Kasuga, Y.Satoh, H.Akai, S.Miyabayashi and T.Toyota.: "Mitochon-drial deoxyribonucleic acid 3256C-T mutation in an Japanese family with noninsulin dependent diabetes mellitus." J Clin Endocrinol Metab. 83. 992-994 (1998)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Y.Horikawa, N.Iwasaki, M.Hara, H.Furuta, Y.Hinokio, B.Cockburn, T.Lindner, K.Yamagata, M.Ogata, O.Tomonaga, H.Kuroki, T.Kasahara, Y.Iwamoto and G.Bell.: "Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associate with MODY" Nature Genet. 17. 384-385 (1998)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Y.Suzuki, T.Muramatsu, M.Taniyama, Y.Goto, Y.Oka, S.Suzuki, K.Tsukuda, Y.Atsumi, I.Nonaka, K.Hosokawa, A.Shimada, T.Asahina and K.Matsuoka: "No assciation of ALDH2 genotype in MELAS" Diabetologia. 40. 1241-1242 (1997)
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Publications] H.Furuta, N.Iwasaki, N.Oda, Y.Hinokio, Y.Horikawa, K.Yamagata, N.Yano, J.Sugahiro, M.Ogata, H.Ohgawara, Y.Omori, Y.Iwamoto and G.Bell.: "Organization and partial sequence of the hepatocyte nuclear factor-4alpha/MODY1 gene and identification of a missense mutation, R127W,in a Japanese family with MODY" Diabetes. 46. 1652-1657 (1997)
Description
「研究成果報告書概要(欧文)」より
-
