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Subcellular localization of sterol biosynthesis enzymes.
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2018-12-08 , DOI: 10.1007/s10735-018-9807-y Katalin Koczok 1, 2 , Channabasavaiah B Gurumurthy 3 , István Balogh 2 , Zeljka Korade 4 , Károly Mirnics 1
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2018-12-08 , DOI: 10.1007/s10735-018-9807-y Katalin Koczok 1, 2 , Channabasavaiah B Gurumurthy 3 , István Balogh 2 , Zeljka Korade 4 , Károly Mirnics 1
Affiliation
Cholesterol synthesis is a complex, coordinated process involving a series of enzymes. As of today, our understanding of subcellular localization of cholesterol biosynthesis enzymes is far from complete. Considering the complexity and intricacies of this pathway and the importance of functions of DHCR7, DHCR24 and EBP enzymes for human health, we undertook a study to determine their subcellular localization and co-localization. Using expression constructs and antibody staining in cell cultures and transgenic mice, we found that all three enzymes are expressed in ER and nuclear envelope. However, their co-localization was considerably different across the cellular compartments. Furthermore, we observed that in the absence of DHCR7 protein, DHCR24 shows a compensatory upregulation in a Dhcr7−/− transgenic mouse model. The overall findings suggest that the sterol biosynthesis enzymes might not always work in a same functional complex, but that they potentially have different, multifunctional roles that go beyond the sterol biosynthesis pathway. Furthermore, the newly uncovered compensatory mechanism between DHCR7 and DHCR24 could be of importance for designing medications that would improve cholesterol production in patients with desmosterolosis and Smith–Lemli–Opitz syndrome.
中文翻译:
甾醇生物合成酶的亚细胞定位。
胆固醇合成是一个复杂的、协调的过程,涉及一系列酶。时至今日,我们对胆固醇生物合成酶的亚细胞定位的理解还远未完成。考虑到该途径的复杂性和复杂性以及 DHCR7、DHCR24 和 EBP 酶的功能对人类健康的重要性,我们进行了一项研究以确定它们的亚细胞定位和共定位。在细胞培养物和转基因小鼠中使用表达构建体和抗体染色,我们发现所有三种酶都在 ER 和核包膜中表达。然而,它们的共定位在细胞隔间有很大不同。此外,我们观察到在没有 DHCR7 蛋白的情况下,DHCR24 在 Dhcr7 中显示出补偿性上调- /-转基因小鼠模型。总体研究结果表明,甾醇生物合成酶可能并不总是在相同的功能复合物中起作用,但它们可能具有超出甾醇生物合成途径的不同的多功能作用。此外,新发现的 DHCR7 和 DHCR24 之间的代偿机制对于设计可改善去骨甾醇症和 Smith-Lemli-Opitz 综合征患者胆固醇产生的药物可能具有重要意义。
更新日期:2018-12-08
中文翻译:
甾醇生物合成酶的亚细胞定位。
胆固醇合成是一个复杂的、协调的过程,涉及一系列酶。时至今日,我们对胆固醇生物合成酶的亚细胞定位的理解还远未完成。考虑到该途径的复杂性和复杂性以及 DHCR7、DHCR24 和 EBP 酶的功能对人类健康的重要性,我们进行了一项研究以确定它们的亚细胞定位和共定位。在细胞培养物和转基因小鼠中使用表达构建体和抗体染色,我们发现所有三种酶都在 ER 和核包膜中表达。然而,它们的共定位在细胞隔间有很大不同。此外,我们观察到在没有 DHCR7 蛋白的情况下,DHCR24 在 Dhcr7 中显示出补偿性上调- /-转基因小鼠模型。总体研究结果表明,甾醇生物合成酶可能并不总是在相同的功能复合物中起作用,但它们可能具有超出甾醇生物合成途径的不同的多功能作用。此外,新发现的 DHCR7 和 DHCR24 之间的代偿机制对于设计可改善去骨甾醇症和 Smith-Lemli-Opitz 综合征患者胆固醇产生的药物可能具有重要意义。