中国医科大学学报

中国医科大学学报

中国医科大学学报 ›› 2012, Vol. 41 ›› Issue (5): 405–408.

• 基础医学 • 上一篇    下一篇

卵磷脂胆固醇酰基转移酶缺陷症LCATG179R突变的初步研究

王晓黎1,王冬冬2,张锦1   

  1. 中国医科大学1.附属第一医院内分泌科,沈阳 110001;2.附属盛京医院妇产科,沈阳 110004
  • 收稿日期:2012-09-27 修回日期:2012-09-27 出版日期:2012-05-20 发布日期:2012-09-27

Mutation (G179R) in LCAT Can Cause the Inactivity of the Enzyme

WANG Xiao-li 1,WANG Dong-dong 2,ZHANG Jin 1   

  1. 1. Department of Endocrinology,The First Hospital,China Medical University,Shenyang 110001, China; 2. Department of Gynecology and Obstetrics, Shengjing Hospital, China Medical University, Shenyang 110004, China
  • Received:2012-09-27 Revised:2012-09-27 Online:2012-05-20 Published:2012-09-27

摘要: 目的 研究1个新近发现的卵磷脂胆固醇酰基转移酶(LCAT)突变型LCATG179R对其编码蛋白正常功能的影响。方法 构建LCAT cDNA野生型和突变型表达载体,通过在HEK293细胞中瞬时表达,测定细胞合成的LCAT的活性,并通过实时定量PCR测定内质网应激相关基因的表达情况。结果 成功构建载体,野生型LCAT酶活力明显高于突变型LCATG179R,且表达突变型LCATG179R的细胞的内质网应激相关基因表达量明显升高。结论 LCAT突变型G179R会导致该酶的活力降低,可能与该突变型蛋白的异常结构有关。携带此种基因突变的患者有患LCAT缺陷症的可能。

关键词: 卵磷脂胆固醇酰基转移酶, 基因突变, 高密度脂蛋白胆固醇, 内质网应激

Abstract: Objective To study the function of G179R, a novel mutation, in Lecithin-cholesterol acyltransferase (LCAT). Methods LCAT cDNA expression vectors were constructed. With transient expression in vitro, the enzyme activity of LCAT was detected. Endoplasmic reticulum stress (ER stress) related gene was detected by real-time PCR. Results LCAT cDNA expression vectors were constructed successfully. Enzyme activity of mutant LCAT was significantly decreased. ER stress related gene expression was significantly decreased in cells which were transfected with mutant LCAT. Conclution Mutant LCAT (G179R) can cause the inactivity of the enzyme, which may cause the dysfunction of the enzyme and clinically cause the LCAT deficiency.

Key words: lecithin-cholesterol acyltransferase, gene mutation, high density lipoprotein cholesterol, ER stress

中图分类号: 

  • Q343.1+3
[1] Jonas A. Lecithin cholesterol acyltransferase[J]. Biochim Biophys Acta, 2000, 1529(1-3):245-256.
[2] Kuivenhoven JA, Pritchard H, Hill J, et al. The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes[J]. J lipid Res, 1997, 38(2):191-205.
[3] Norum KR, Gjone E. Familial plasma lecithin:cholesterol acyltransferase deficiency. Biochemical study of a new inborn error of metabolism[J]. Stand J ClinLab Invest, 1967, 22(4):231-243.
[4] Peelman F, Verschelde JL, Vanloo B, et al. Effects of natural mutations in lecithin:cholesterol acyltransferase on the enzyme structure and activity[J]. J Lipid Res, 1999, 40(1):59-69.
[5] Frasca GM, Soverini L, Tampieri E, et al. A 33-year-old man with nephrotic syndrome and lecithin¨Ccholesterol acyltransferase (LCAT) deficiency. Description of two new mutations in the LCAT gene[J]. Nephrol Dial Transplant, 2004, 19(6):1622-1624.
[6] Wang XL, Osuga J, Tazoe F, et al.. Molecular analysis of a novel LCAT mutation (Gly179→Arg ) found in a patient with a complete LCAT deficiency. J Atheroscler Thromb[J], 2011, 18(8): 713-719.
[7] Chisholm JW, Gebre AK, Parks JS. Characterization of C-terminal histidine-tagged human recombinant lecithin:cholesterol acyltransferase[J]. J Lipid Res, 1999,40(8):1512-1519.
[8] Bujo H, Kusunoki J, Ogasawara M, et al. Molecular defect in familial lecithin: cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease[J]. Biochem Biophys Res Commun, 1991, 181(3):933-940.
[9] Gotoda T, Yamada N, Murase T, et al. Differential phenotypic expression by three mutant alleles in familial lecithin: cholesterol acyltransferase deficiency[J]. Lancet, 1991, 338(8770):778-781.
[10] Calabresi L, Pisciotta L, Costantin A, et al. The molecular basis of lecithin: cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families[J]. Arterioscler Thromb Vasc Biol, 2005, 25(9):1972-1978.
[11]Hollevoom AG, Kuivenhoven JA, van Olden CC, et al. Proteinuria in early childhood due to familial LCAT deficiency caused by loss of a disulfide bond in lecithin:cholesterol acyl transferase[J]. Atherosclerosis,2011,216(1):161-165.
[12] Peelman F, Goethals M, Vanloo B, et al. Structural and functional properties of the 154-171 wild-type and variant peptides of human lecithin-cholesterol acyltransferase[J]. Eur J Biochem, 1997, 249(3):708-715.
[13] Ollis DL, Cheah E, Cygler M, et al. The α/β hydrolase fold[J]. Protein Eng,1992, 5(3):197-211.
[14] Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls[J]. Genes Dev, 1999,13(10):1211-1233.
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