PHOTOSENSITIZED KILLING OF CULTURED FIBROBLASTS FROM PATIENTS WITH PEROXISOMAL DISORDERS DUE TO PYRENE FATTY-ACID MEDIATED ULTRAVIOLET DAMAGE
PHOTOSENSITIZED KILLING OF CULTURED FIBROBLASTS FROM PATIENTS WITH PEROXISOMAL DISORDERS DUE TO PYRENE FATTY-ACID MEDIATED ULTRAVIOLET DAMAGE
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DOI：
10.1172/jci115509
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发表时间：
1991-12-01
影响因子：
15.9
通讯作者：
MOSER, HW
中科院分区：
文献类型：
--
作者：
HOEFLER, G;PASCHKE, E;MOSER, HW
在来自五种过氧化物酶体疾病患者的培养成纤维细胞中研究了芘脂肪酸对细胞对紫外线 (UV) 辐射的抵抗力的影响。与对照相比，所有这些都显示出存活率降低。效果随所涉及的生化缺陷和芘脂肪酸的链长而变化。在缺乏缩醛磷脂（点状根茎软骨发育不良）的细胞和缺乏过氧化物酶体脂肪酸氧化（双功能酶缺乏）的细胞中观察到存活率降低，这些细胞会积累芘脂肪酸。 X连锁肾上腺脑白质营养不良成纤维细胞积累芘脂肪酸，并且仅当暴露于长链芘脂肪酸时才表现出增加的紫外线敏感性。在缩醛磷脂合成和脂肪酸氧化联合受损的细胞（齐薇格综合征、新生儿肾上腺脑白质营养不良）中，紫外线辐射抵抗力最低，这表明紫外线敏感性与缩醛磷脂与自由基产生物质的比例成反比。缺乏缩醛磷脂的成纤维细胞，当其缩醛磷脂水平通过十六烷基甘油正常化时，获得了正常的紫外线抵抗力。当Zellweger细胞与X连锁肾上腺脑白质营养不良细胞融合时，以及当属于不同互补组的Zellweger细胞融合时，紫外线抵抗力增加。该结果提供了与过氧化物酶体疾病相关的多种畸形的发病机制，以及选择代谢缺陷已得到纠正的细胞的方法。
The influence of pyrene-fatty acids on the resistance of cells to ultraviolet (UV) radiation was investigated in cultured fibroblasts from patients with five types of peroxisomal disorders. All showed reduced survival compared to control. The effect varied with the biochemical defect involved and the chain length of the pyrene fatty acid. Reduced survival was observed in cells deficient in plasmalogens (rhizomelic chondrodysplasia punctata) and in cells deficient in peroxisomal fatty acid oxidation (bifunctional enzyme deficiency), which accumulated pyrene-fatty acids. X-linked adrenoleukodystrophy fibroblasts accumulated pyrene-fatty acids and showed increased UV sensitivity only when exposed to longer-chain pyrene fatty acids. UV radiation resistance was lowest in cells with combined impairment of plasmalogen synthesis and fatty acid oxidation (Zellweger syndrome, neonatal adrenoleukodystrophy), suggesting that UV sensitivity correlates inversely with the ratio of plasmalogens to radical producing substances.Fibroblasts deficient in plasmalogens gained normal UV resistance when their plasmalogen levels were normalized by hexadecylglycerol. UV resistance increased when Zellweger cells were fused with X-linked adrenoleukodystrophy cells, and also when Zellweger cells belonging to different complementation groups were fused.The results provide leads to the pathogenesis of the multiple malformations associated with peroxisomal disorders and a method for the selection of cells in which the metabolic defect has been corrected.