INCREASED LIPID PEROXIDATION IN PATIENTS WITH ACERULOPLASMINEMIA

针鸟血浆血症患者脂质过氧化增加

• 批准号: 08670702
• 负责人: MIYAJIMA Hiroaki
• 金额: $ 1.41万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-08670702/
• 关键词: CERULOPLASMIN; LIPID PEROXIDATION; IRON; VERY LONG-CHAIN FATTY ACID; PEROXISOME; FREE RADICAL; GENE MUTATION; IRON CHELATOR; セルロプラスミン欠損症

Aceruloplasminemia is a newly recognized autosomal recessive disorderof iron metabolism resulting in neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. Clinically it is recognized as a triad of diabetes, retinal degeneration and neurologic disease. This disease is characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, low serum iron concentration, and iron accumulation in the brain, liver, and other tissues. Iron is an important catalyst of oxyradical-mediated cellular and tissue injury. We report here on the identification of increased lipid peroxidation in the plasma and erythrocyte membranes of affected family members with aceruloplasminemia. Plasma lipid peroxidation was determined as thiobarbituric acid-reactive products (TBA products) in plasma samples from twenty controls, eight heterozygotes, and three homozygotes. The level of lipid peroxides was three times greater in homozygous patients and an inverse relation w … More as found between ceruloplasmin concentrations and quantitative estimates of TBA products (r=-0.9l5 : p<0.01). Profile of fatty acids in the erythrocyte membranes was examined by gas chromatography-mass spectrometry. We found accumulation of very-long-chain fatty acids, cis-17-hexacosenoic acid (C26 : 1) and hexacosanoic acid (C26 : 0), in the blood cells of aceruloplasminemia patients. The ratios of C26 : 1/C22 : 0 and C26 : 0/C22 : 0 were also elevated. In addition, a marked excess in the alpha-hydroxy fatty acids [alpha-hydroxydocosanoic acid (hC22 : 0), alpha-hydroxytricosanoic acid (hC23 : 0), alpha-hydroxytetracosanoic acid (hC24 : 0), and alpha-hydroxytetracosenoicacid (hC24 : 1)] was also detected in these cells. It is likely that free radicals generated in patients with aceruloplasminemia may interrupt the peroxisomal beta-oxidation of fatty acids, and may result in lipid hydrolysis during lipid peroxidation in the erythrocyte membrane. Taken together these data suggest that increased susceptibility to lipid peroxidation in plasma and the erythrocyte membrane may contribute to the unique neuropathology observed in patients with acerul oplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia. Less

血浆无铜蓝蛋白血症是一种新发现的常染色体隐性遗传性铁代谢紊乱，可导致视网膜和基底节神经变性以及糖尿病。临床上它被认为是糖尿病、视网膜变性和神经系统疾病的三联征。这种疾病的特征是血浆铜蓝蛋白基因突变，血清铜蓝蛋白缺乏，血清铁浓度低，以及脑、肝和其他组织中的铁积累。铁是氧自由基介导的细胞和组织损伤的重要催化剂。我们在这里报告的鉴定增加脂质过氧化作用的血浆和红细胞膜的受影响的家庭成员与aceroplasminemia。血浆脂质过氧化测定为硫代巴比妥酸反应产物（TBA产品）的血浆样本从20个控制，8个杂合子，和3个纯合子。在纯合子患者中，脂质过氧化物的水平高出3倍，与基因型呈负相关。 ...更多信息 铜蓝蛋白浓度与TBA产物的定量估计值之间存在相关性（r=-0.915：p<0.01）。用气相色谱-质谱联用仪检测红细胞膜脂肪酸的分布。我们发现蓄积的极长链脂肪酸，顺式-17-二十六碳烯酸（C26：1）和二十六碳烯酸（C26：0），在血细胞浆细胞积患者。C26：1/C22：0和C26：0/C22：0比值也升高。此外，在这些细胞中还检测到α-羟基脂肪酸[α-羟基二十二烷酸（hC 22：0）、α-羟基二十三烷酸（hC 23：0）、α-羟基二十四烷酸（hC 24：0）和α-羟基二十四碳烯酸（hC 24：1）]显著过量。浆细胞球蛋白血症患者体内产生的自由基可能会中断脂肪酸的过氧化物酶体β-氧化，并可能导致红细胞膜脂质过氧化过程中的脂质水解。总之，这些数据表明，血浆和红细胞膜中脂质过氧化的易感性增加可能有助于在acerul oplasminemia患者中观察到的独特神经病理学，并暗示自由基介导的组织损伤在基底神经节退行性疾病中的作用。少

项目成果

Hiroaki Miyajima: "Increased very long-diain fatty acids in eryturocyte membranes of patients with aceruliplasminemia" Neurology. 50・1. 130-136 (1998)

Hiroaki Miyajima：“铜蓝蛋白血症患者的红细胞膜中的长链脂肪酸增加”，《神经病学》50・1（1998）。

Miyajima H,Takahashi Y,Shimizu H,Sakai N,Kamata T,Kaneko E: "Late onset diabetes mellitus in patients with hereditary aceruloplasminemia. (Editorial review, 596-597)" Int Med. 35. 641-645 (1996)

Miyajima H、Takahashi Y、Shimizu H、Sakai N、Kamata T、Kaneko E：“遗传性铜蓝蛋白血症患者的迟发性糖尿病。（编辑评论，596-597）” Int Med。

Miyajima H,Takahashi Y,Kamata T,Shimizu H,Sakai N,Gitlin JD: "Use of desferrioxamine in the treatment of aceruloplasminemia." Ann Neurol. 41. 404-407 (1997)

Miyajima H、Takahashi Y、Kamata T、Shimizu H、Sakai N、Gitlin JD：“去铁胺在治疗铜蓝蛋白血症中的用途。”

Miyajima H,Adachi J,Tatsuno Y,Takahashi Y,Fujimoto M,Kaneko E,Gitlin JD: "Increased very-long-chain fatty acids in erythrocyte membranes of patients with aceruloplasminemia." Neurology. 50. 130-136 (1998)

Miyajima H、Adachi J、Tatsuno Y、Takahashi Y、Fujimoto M、Kaneko E、Gitlin JD：“铜蓝蛋白血症患者红细胞膜中的极长链脂肪酸增加。”

Hiroaki Miyajima: "Increased plasma lipid peroxidation in patients with aceruloplasminemia" Free Radic.Biol.Med.20・5. 757-760 (1996)

Hiroaki Miyajima：“铜蓝蛋白血症患者血浆脂质过氧化增加”Free Radic.Biol.Med.20・5（1996）。