Role of 3-deoxyglucosone in the pathogenesis of uremic and diabetic complications

3-脱氧葡萄糖醛酮在尿毒症和糖尿病并发症发病机制中的作用

• 批准号: 08457287
• 负责人: NIWA Toshimitsu
• 金额: $ 0.64万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457287/
• 关键词: 3-deoxyglucosone; imidazolone; uremia; diabetes mellitus; amyloid; AGE; カルボキシメチルリシン; 糖尿病性腎症; 透析アミロイドーシス; 動脈硬化; メイラード反応

3-Deoxyglucosone (3-DG) is a reactive intermediate of the Maillard reaction which is a nonenzymatic glycation reaction of proteins. To investigate the role of 3-DG in the pathogenesis of uremic and diabetic complications, we produced and anti-AGE antibody (AG-1) that reacted specifically with imidazolone, a novel advanced glycation end products (AGE). The imidazolone is the reaction products of the guanidino group of arginine with 3-DG.We demonstrated that amyloid tissue beta_2m is modified with imidazolone in patients with DRA.Further, we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in advanced stage of diabetic nephropathy as well as in atherosclerotic lesions of aortas. These results, taken together with a recent demonstration of increased serum 3-DG levels in uremia and diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term uremic and diabetic complications such as dialysis-related amyloidosis, and diabetic nephropathy and atherosclerosis.

3-脱氧葡萄糖苷(3-DG)是蛋白质的非酶糖基化反应，是美拉德反应的反应中间体。为了探讨3-DG在尿毒症和糖尿病并发症发病机制中的作用，我们制备了抗AGE抗体(AG-1)，并与新型晚期糖基化终产物(AGE)咪唑酮发生特异性反应。咪唑酮是精氨酸胍基团与3-DG反应的产物。我们证实了DRA患者淀粉样蛋白组织β_2m被咪唑酮修饰。此外，我们用该抗体免疫组织化学方法研究了咪唑酮在糖尿病患者肾脏和主动脉中的定位。在糖尿病肾病晚期的肾小球结节病变、肾小球系膜基质扩张、肾动脉及动脉粥样硬化病变中均可检测到特异性的咪唑酮免疫反应。这些结果，加上最近尿毒症和糖尿病患者血清3-DG水平升高的证据，有力地表明，3-DG产生的咪唑酮可能有助于尿毒症和糖尿病长期并发症的进展，如透析相关的淀粉样变性、糖尿病肾病和动脉粥样硬化。

项目成果

丹羽利充: "β2-Microglobulin dialysis amyloid and its formation: role of 3-deoxyglucosone and advanced glycation end products." Nephron. 76. 373-391 (1997)

Toshimitsu Niwa：“β2-微球蛋白透析淀粉样蛋白及其形成：3-脱氧葡萄糖酮和晚期糖基化终产物的作用。” 76. 373-391 (1997)

Niwa T,Katsuzaki T,Ishizaki Y,Hayase F,Miyazaki T,Uematsu T,Tatemichi N,Takei Y.: "Imidazolone, a novel advanced glycation end product, is present at high lovels in kidneys of rats with streptozotocin-induced diabetes." FEBS Lett. 407. 297-302 (1997)

Niwa T、Katsuzaki T、Ishizaki Y、Hayase F、Miyazaki T、Uematsu T、Tatemichi N、Takei Y.：“咪达唑酮是一种新型的晚期糖基化终产物，在链脲佐菌素诱导的糖尿病大鼠的肾脏中存在大量存在。

Niwa T.: "beta2-Microglobulin dialysis amyloid and its formation : role of 3-deoxyglucosone and advanced glycation end products." Nephron. 76. 373-391 (1997)

Niwa T.：“β2-微球蛋白透析淀粉样蛋白及其形成：3-脱氧葡萄糖酮和晚期糖基化终产物的作用。”

Niwa T,et al.: "Amyloid β2-microglobulin is modified with N'-(carboxymethyl) lysine in dialysis-related amyloidosis." Kidney Int. 50. 1303-1309 (1996)

Niwa T 等人：“在透析相关淀粉样变性中用 N-（羧甲基）赖氨酸修饰淀粉样蛋白 β2-微球蛋白。”50. 1303-1309 (1996)

丹羽 利充: "Immunohistochemical detection of imidazolone,a novel advanced glycation end product,it kidneys and aortas of diabetic patients." J Clin Invest. 99. 1272-1280 (1997)

Toshimitsu Niwa：“咪唑酮的免疫组织化学检测，一种新型晚期糖基化终产物，它对糖尿病患者的肾脏和主动脉而言。” J Clin Invest。