丁酸类似物增强新生儿红系祖细胞中γ珠蛋白基因的表达。

Butryic acid analogues augment gamma globin gene expression in neonatal erythroid progenitors.

作者信息

Perrine S P, Miller B A, Greene M F, Cohen R A, Cook N, Shackleton C, Faller D V

机构信息

Children's Hospital Oakland Research Institute, California.

出版信息

Biochem Biophys Res Commun. 1987 Oct 29;148(2):694-700. doi: 10.1016/0006-291x(87)90932-6.

DOI:10.1016/0006-291x(87)90932-6

PMID:3689367

Abstract

The gamma----beta globin gene switch in humans is normally on a set developmental clock but is delayed in infants of diabetic mothers. We cultured cord blood erythroid progenitors and assayed globin produced in the presence and absence of metabolites that are elevated in such infants. Analogues of butyric acid at supranormal concentrations significantly augmented gamma and inhibited beta globin expression. The uptake of alpha-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of alpha-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting gamma globin expression in the beta globin chain diseases.

摘要

人类的γ-珠蛋白基因转换通常遵循特定的发育时钟，但在糖尿病母亲的婴儿中会延迟。我们培养了脐血红细胞祖细胞，并检测了在这类婴儿中浓度升高的代谢产物存在和不存在时所产生的珠蛋白。超正常浓度的丁酸类似物显著增加了γ珠蛋白并抑制了β珠蛋白的表达。在超正常胰岛素存在的情况下，α-氨基-n-丁酸进入集落衍生红细胞的摄取增加。这些发现表明，发育中的胎儿体内α-氨基-n-丁酸和胰岛素水平升高会延迟珠蛋白转换，并可能为增加β珠蛋白链疾病中的γ珠蛋白表达提供潜力。