INCREASED LIPID PEROXIDATION IN PATIENTS WITH ACERULOPLASMINEMIA

紫纤溶酶血症是一种新近发现的常染色体隐性铁代谢疾病，可导致视网膜和基底神经节的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位一体。这种疾病的特征是铜蓝蛋白基因突变，血清铜蓝蛋白缺失，血清铁浓度低，铁在脑、肝和其他组织中积累。铁是氧化自由基介导的细胞和组织损伤的重要催化剂。我们在此报告的鉴定增加脂质过氧化在血浆和红细胞膜受影响的家庭成员与尖状纤溶酶血症。在20个对照、8个杂合子和3个纯合子的血浆样品中测定血浆脂质过氧化为硫代巴比妥酸反应产物（TBA产物）。纯合子患者的脂质过氧化物水平是纯合子患者的3倍，铜蓝蛋白浓度与TBA产物的定量估计呈负相关（r=-0.9 15: p<0.01）。采用气相色谱-质谱联用法测定红细胞膜脂肪酸谱。我们发现超长链脂肪酸顺式-17-六糖酸（C26: 1）和六糖酸（C26: 0）在乙酰纤溶酶血症患者的血细胞中积累。C26: 1/C22: 0和C26: 0/C22: 0的比值也升高。此外，α -羟基脂肪酸[α -羟基二十二酸（hC22: 0）， α -羟基三糖酸（hC23: 0）， α -羟基四糖酸（hC24: 0）， α -羟基四糖酸（hC24: 1）]在这些细胞中也明显过量。酸纤溶酶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，并可能在红细胞膜脂质过氧化过程中导致脂质水解。综上所述，这些数据表明，血浆和红细胞膜对脂质过氧化的易感性增加可能有助于在尖锐型卵磷脂血症患者中观察到的独特神经病理，并暗示自由基介导的组织损伤在基底节区退行性疾病中的作用。少

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