INCREASED LIPID PEROXIDATION IN PATIENTS WITH ACERULOPLASMINEMIA

无铜蓝蛋白血症是一种新发现的常染色体隐性铁代谢紊乱，可导致视网膜和基底节的神经变性以及糖尿病。在临床上，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、肝和其他组织中积聚。铁是氧自由基介导的细胞和组织损伤的重要催化剂。我们在此报告受影响的无纤维蛋白溶酶血症家系成员血浆和红细胞膜的脂质过氧化增加。以硫代巴比妥酸反应产物(TBA产物)的形式测定了20名对照组、8名杂合子和3名纯合子的血浆脂质过氧化产物。纯合子患者的过氧化脂质水平是纯合子患者的三倍，与…呈负相关铜蓝蛋白浓度与TBA产物定量估计值之间的相关性更强(r=-0.915：P&lt；0.01)。用气相色谱-质谱法分析红细胞膜中的脂肪酸组成。我们发现超长链脂肪酸顺式-17-己二烯酸(C26：1)和十六烷酸(C26：0)在无纤维支原体血症患者的血细胞中积聚。C26：1/C22：0和C26：0/C22：0比值升高。此外，在这些细胞中还检测到显著过量的α-羟基脂肪酸[α-羟基二十二酸(hC22：0)、α-羟基二十二酸(hC23：0)、α-羟基二十四酸(hC24：0)和α-羟基二十四烯酸(hC24：1)]。无纤维蛋白溶酶血症患者体内产生的自由基可能干扰了脂肪酸的过氧化体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。综上所述，这些数据表明，血浆和红细胞膜对脂质过氧化的敏感性增加可能是导致急性血浆纤溶酶血症患者独特的神经病理改变的原因之一，并暗示自由基介导的组织损伤在基底节退行性疾病中发挥了作用。较少

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