Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients.
Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients.
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DOI：
10.3390/ijms22168645
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发表时间：
2021-08-11
影响因子：
5.6
通讯作者：
Yokoyama K
中科院分区：
文献类型：
--
作者：
Fujiwara Y;Hama K;Shimozawa N;Yokoyama K
肾上腺白质营养不良（X-ALD）是一种由atp结合盒亚家族D成员1基因突变引起的x连锁遗传病，该基因编码过氧化物酶体膜蛋白，肾上腺白质营养不良蛋白（ALDP）。ALDP与超长链脂肪酸（VLCFAs，碳链长度≥24）转运到过氧化物酶体有关。ALDP缺陷导致饱和VLCFAs在血浆和组织中积累，从而导致髓磷脂和肾上腺的损伤。在这里，我们分析了X-ALD患者成纤维细胞中的鞘糖脂（GSL）种类。定量分析采用液相色谱-电喷雾电离-手性柱串联质谱法，采用多反应监测（MRM）模式。MRM跃迁设计为扫描长链碱基前体离子以检测GSLs，扫描己糖中性损失以检测己糖神经酰胺（HexCer），扫描磷胆碱前体离子以检测鞘磷脂（SM）。我们的研究结果显示，在X-ALD患者的成纤维细胞中，含有C25和c26的HexCer、Hex2Cer、NeuAc-Hex2Cer、NeuAc-HexNAc-Hex2Cer、Hex3Cer、HexNAc-Hex3Cer和SM的水平升高。总之，我们精确量化了X-ALD患者成纤维细胞中的SM和各种GSLs，并确定了升高的含vlcfa的GSLs的结构信息。
Adrenoleukodystrophy (X-ALD) is an X-linked genetic disorder caused by mutation of the ATP-binding cassette subfamily D member 1 gene, which encodes the peroxisomal membrane protein, adrenoleukodystrophy protein (ALDP). ALDP is associated with the transport of very-long-chain fatty acids (VLCFAs; carbon chain length ≥ 24) into peroxisomes. Defective ALDP leads to the accumulation of saturated VLCFAs in plasma and tissues, which results in damage to myelin and the adrenal glands. Here, we profiled the glycosphingolipid (GSL) species in fibroblasts from X-ALD patients. Quantitative analysis was performed using liquid chromatography–electrospray ionization–tandem mass spectrometry with a chiral column in multiple reaction monitoring (MRM) mode. MRM transitions were designed to scan for precursor ions of long-chain bases to detect GSLs, neutral loss of hexose to detect hexosylceramide (HexCer), and precursor ions of phosphorylcholine to detect sphingomyelin (SM). Our results reveal that levels of C25 and C26-containing HexCer, Hex2Cer, NeuAc-Hex2Cer, NeuAc-HexNAc-Hex2Cer, Hex3Cer, HexNAc-Hex3Cer, and SM were elevated in fibroblasts from X-ALD patients. In conclusion, we precisely quantified SM and various GSLs in fibroblasts from X-ALD patients and determined structural information of the elevated VLCFA-containing GSLs.
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影响因子：
4.7
作者：
IGARASHI, M;SCHAUMBURG, HH;SUZUKI, K
通讯作者：
SUZUKI, K
影响因子：
6
作者：
BUDKA, H;SLUGA, E;HEISS, WD
通讯作者：
HEISS, WD
DOI：
10.1016/b978-0-444-59565-2.00028-9
发表时间：
2013-01-01
期刊：
PEDIATRIC NEUROLOGY, PT III
影响因子：
--
作者：
Aubourg, Patrick;Wanders, Ronald
通讯作者：
Wanders, Ronald
影响因子：
4.6
作者：
Cozma C;Iurașcu MI;Eichler S;Hovakimyan M;Brandau O;Zielke S;Böttcher T;Giese AK;Lukas J;Rolfs A
通讯作者：
Rolfs A
影响因子：
2.9
作者：
Calvano, Cosima Damiana;Ventura, Giovanni;Cataldi, Tommaso R. I.
通讯作者：
Cataldi, Tommaso R. I.