1997 年度実績報告書

腎疾患における高度糖化蛋白の病態生理学的意義に関する共同研究

研究課題

研究課題/領域番号	09044280
研究機関	東海大学
研究代表者	宮田敏男東海大学, 総合医学研究所, 講師 (10222332)
研究分担者	C.VAN Yperse ルバイン大学, 医学部, 教授 BAYNES John サウスカロライナ大学, 医学部, 教授 STERN Daivid コロンビア大学, 細胞性理学部教授, 教授 MONNIER Vinc ケースウエスタンリザーブ大学, 病理研究所, 教授
キーワード	酸化ストレス / カルボニルストレス / AGEs / 腎不全 / レドックス制御 / 糖尿病 / ペントシジン
研究概要	酸化ストレスに対するレドックス制御は、細胞さらには生体のホメオスターシスの維持に重要な役割を演じている。生体に存在する糖や脂質は、酸化ストレス下において反応性の高いカルボニル化合物に変化し、非酵素的に蛋白のアミノ基や核酸等を修飾して、advanced glycation/lipidation end products(AGEs/ALEs)、advanced glycoxidation products(COPs)、lipid peroxidation products(LLPs)等が生成する。当研究室では、AGEs及びGOPsであるペントシジン、AGEs及びALEsであるカルボキシメチルリジン(CML)、LLPsであるマロンジアルデヒド(MDA)、ALEsであるヒドロキシノネナ-ル(HNE)について化学的分析法あるいは特異的な抗体を用いた免疫学的測定法を確立し、これら疾患のマーカーとしての可能性について検討した。その結果、腎不全等の酸化ストレスが亢進している病態においてカルボニル化合物やその蛋白修飾物の生成が亢進していることを明らかにした。また、糖尿病患者においては、血中ペントシジン値が糖尿病の循環器合併症のマーカーとなる可能性を見いだした。免疫組織学的検討の結果、動脈硬化、糖尿病あるいは腎不全合併症、アルツハイマー病等の病変部に一致してペントシジン、CML、MDAおよびHNEが存在し、これら蛋白修飾物が組織障害に重要な役割を演じていることが示唆された。さらに、腎不全患者血中にペントシジンが著しく蓄積するメカニズムについて検討を行ったところ、腎不全患者血清中には反応性の高いカルボニル化合物の蓄積があり、蛋白修飾亢進すなわちカルボニルストレス状態にありAGEsの産生が促進している可能性が示唆された。また、カルボニルストレスにはsuperoxide dismutase(SOD)ならびにglutathione peroxidase等の抗酸化酵素のimbalanceが関与することも示した。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Toshio Niyata: "Advanced glycation end products ebhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted with devitalized bone particles" J Am Soc Nephrol. 260-270 (1997)
[文献書誌] Toshio Miyata: "Oxidation conspires with glycation to create noxious advanced glycation end products in renal failure" Nephrol Dial Transplant. 12. 255-258 (1997)
[文献書誌] Toshio Miyata: "Clearance of pentosidine,an advanced glycation end product,by different modalities of renal replacement therapy" Kidney International. 51. 881-887 (1997)
[文献書誌] Toshio Miyata: "Implication of redox imbalance in accelerated formation of advanced glycation end products in renal failure patients." Kidney International. 51. 1170-1181 (1997)
[文献書誌] Toshio Miyata: "Immunohistochemical localization of advanced glycation end products,pentosidine and carboxymetyllysine,inlipofuscin pigments of alzheimer's discase and aged neurons" Biochem Biophys Res Commun. 232. 327-332 (1997)
[文献書誌] Toshio Miyata: "Protein modification by a Maillard reaction intermediate methylglyoxal immunochemical detection of fluorescent 5-methylimidazolone derivatives in vivo." FEBS Letter. 410. 313-318 (1997)
[文献書誌] Toshio Miyata: "Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells." Biochem Biophys Res Commun. 239. 111-115 (1997)
[文献書誌] Toshio Miyata: "Funcional quantiative analysis of the genome in cultured human mesangial cells." Kidney International. 53. 154-158 (1998)
[文献書誌] Toshio Miyata: "Renal catabolism of advanced glycation end products : the fate of pentosidne." Kidney International. 53. 416-422 (1998)
[文献書誌] Toshio Miyata: "Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions." J Clin Invest. 100. 29954-3004 (1997)
[文献書誌] Toshio Miyata: "β2-microgloburin in kidney disease." J Am Soc Nephrol. (in press).
[文献書誌] Toshio Miyata: "Oxidative stress and long-term complications of uremia." Kidney International. (in press).
[文献書誌] Toshio Miyata: "β2-microgloburin in kidney disease." J Am Soc Nephrol. (in press).
[文献書誌] Toshio Miyata: "Advanced glycation end products and carbonyl stress." J Art Org. (in press).
[文献書誌] Toshio Miyata: "Renal catabolism of advanced glycation end products : the fate of pentosidne." Kidney International. (in press).
[文献書誌] Toshio Miyata: "Immunohistochemical colocalization of glycoxidation producrs and lipid peroxidation products in diabetic renal glomerular lesions" J Clin Invest. (in press).
[文献書誌] Toshio Miyata: "Increased pentosidine,an davanced glycation end products,in plasma and synovial fluid from parients with rheumatoid arthritis and its relation with markers of inflammation." Biochem Biophys Res Commun. (in press).
[文献書誌] Toshio Miyata: "Altered non-enzymatic biochemistry in uremia involving carbohydrates and lipids." Nephrol Dial Transplant. (in press).

1997 年度 実績報告書

腎疾患における高度糖化蛋白の病態生理学的意義に関する共同研究

研究代表者

宮田 敏男 東海大学, 総合医学研究所, 講師 (10222332)

研究成果

[文献書誌] Toshio Niyata: "Advanced glycation end products ebhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted with devitalized bone particles" J Am Soc Nephrol. 260-270 (1997)

[文献書誌] Toshio Miyata: "Oxidation conspires with glycation to create noxious advanced glycation end products in renal failure" Nephrol Dial Transplant. 12. 255-258 (1997)

[文献書誌] Toshio Miyata: "Clearance of pentosidine,an advanced glycation end product,by different modalities of renal replacement therapy" Kidney International. 51. 881-887 (1997)

[文献書誌] Toshio Miyata: "Implication of redox imbalance in accelerated formation of advanced glycation end products in renal failure patients." Kidney International. 51. 1170-1181 (1997)

[文献書誌] Toshio Miyata: "Immunohistochemical localization of advanced glycation end products,pentosidine and carboxymetyllysine,inlipofuscin pigments of alzheimer's discase and aged neurons" Biochem Biophys Res Commun. 232. 327-332 (1997)

[文献書誌] Toshio Miyata: "Protein modification by a Maillard reaction intermediate methylglyoxal immunochemical detection of fluorescent 5-methylimidazolone derivatives in vivo." FEBS Letter. 410. 313-318 (1997)

[文献書誌] Toshio Miyata: "Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells." Biochem Biophys Res Commun. 239. 111-115 (1997)

[文献書誌] Toshio Miyata: "Funcional quantiative analysis of the genome in cultured human mesangial cells." Kidney International. 53. 154-158 (1998)

[文献書誌] Toshio Miyata: "Renal catabolism of advanced glycation end products : the fate of pentosidne." Kidney International. 53. 416-422 (1998)

[文献書誌] Toshio Miyata: "Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions." J Clin Invest. 100. 29954-3004 (1997)

[文献書誌] Toshio Miyata: "β2-microgloburin in kidney disease." J Am Soc Nephrol. (in press).

[文献書誌] Toshio Miyata: "Oxidative stress and long-term complications of uremia." Kidney International. (in press).

[文献書誌] Toshio Miyata: "β2-microgloburin in kidney disease." J Am Soc Nephrol. (in press).

[文献書誌] Toshio Miyata: "Advanced glycation end products and carbonyl stress." J Art Org. (in press).

[文献書誌] Toshio Miyata: "Renal catabolism of advanced glycation end products : the fate of pentosidne." Kidney International. (in press).

[文献書誌] Toshio Miyata: "Immunohistochemical colocalization of glycoxidation producrs and lipid peroxidation products in diabetic renal glomerular lesions" J Clin Invest. (in press).

[文献書誌] Toshio Miyata: "Increased pentosidine,an davanced glycation end products,in plasma and synovial fluid from parients with rheumatoid arthritis and its relation with markers of inflammation." Biochem Biophys Res Commun. (in press).

[文献書誌] Toshio Miyata: "Altered non-enzymatic biochemistry in uremia involving carbohydrates and lipids." Nephrol Dial Transplant. (in press).

1997 年度実績報告書

宮田敏男東海大学, 総合医学研究所, 講師 (10222332)