Butryic acid analogues augment γ globin gene expression in neonatal erythroid progenitors

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

doi:10.1016/0006-291X(87)90932-6

Butryic acid analogues augment γ globin gene expression in neonatal erythroid progenitors

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

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Abstract

The γ→β 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 γ and inhibited β globin expression. The uptake of α-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of α-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting γ globin expression in the β globin chain diseases.

Original language	English (US)
Pages (from-to)	694-700
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	148
Issue number	2
DOIs	https://doi.org/10.1016/0006-291X(87)90932-6
State	Published - Oct 29 1987

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Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/0006-291X(87)90932-6

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@article{656cbee348f54e4389f031da4282720e,

title = "Butryic acid analogues augment γ globin gene expression in neonatal erythroid progenitors",

abstract = "The γ→β 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 γ and inhibited β globin expression. The uptake of α-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of α-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting γ globin expression in the β globin chain diseases.",

author = "Perrine, {S. P.} and Miller, {B. A.} and Greene, {M. F.} and Cohen, {R. A.} and N. Cook and C. Shackleton and Faller, {D. V.}",

note = "Funding Information: by Grant HL-37118 from the National Heart, Lung, and Blood and by a grant from the Juvenile Diabetes Foundation Dr. Miller is the recipient of a Clinical Investigator Natlonal Heart, Lung, and Blood Institute. Dr. Faller 1s of a Senior Faculty Award from the American Cancer Society.",

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doi = "10.1016/0006-291X(87)90932-6",

language = "English (US)",

volume = "148",

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T1 - Butryic acid analogues augment γ globin gene expression in neonatal erythroid progenitors

AU - Perrine, S. P.

AU - Miller, B. A.

AU - Greene, M. F.

AU - Cohen, R. A.

AU - Cook, N.

AU - Shackleton, C.

AU - Faller, D. V.

N1 - Funding Information: by Grant HL-37118 from the National Heart, Lung, and Blood and by a grant from the Juvenile Diabetes Foundation Dr. Miller is the recipient of a Clinical Investigator Natlonal Heart, Lung, and Blood Institute. Dr. Faller 1s of a Senior Faculty Award from the American Cancer Society.

PY - 1987/10/29

Y1 - 1987/10/29

N2 - The γ→β 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 γ and inhibited β globin expression. The uptake of α-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of α-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting γ globin expression in the β globin chain diseases.

AB - The γ→β 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 γ and inhibited β globin expression. The uptake of α-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of α-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting γ globin expression in the β globin chain diseases.

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Butryic acid analogues augment γ globin gene expression in neonatal erythroid progenitors

Abstract

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