Research article summary (published 18 Apr 2009):

Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive erythroid cells.

Full Abstract

Short-chain fatty acids (SCFAs; butyrate and propionate) up-regulate embryonic/fetal globin gene expression through unclear mechanisms. In a murine model of definitive erythropoiesis, SCFAs increased embryonic beta-type globin gene expression in primary erythroid fetal liver cells (eFLCs) after 72 hours in culture, from 1.7% (+/- 1.2%) of total beta-globin gene expression at day 0 to 4.9% (+/- 2.2%) in propionate and 5.4% (+/- 3.4%) in butyrate; this effect was greater in butyrate plus insulin/erythropoietin (BIE), at 19.5% (+/- 8.3%) compared with 0.1% (+/- 0.1%) in ins/EPO alone (P < .05). Fetal gamma-globin gene expression was increased in human transgene-containing eFLCs, to 35.9% (+/- 7.0%) in BIE compared with 4.4% (+/- 4.2%) in ins/EPO only (P < .05). Embryonic globin gene expression was detectable in 11 of 15 single eFLCs treated with BIE, but in0 of 15 ins/EPO-only treated cells. Butyrate-treated [65.5% (+/- 9.9%)] and 77.5% (+/- 4.0%) propionate-treated eFLCs were highly differentiated in culture, compared with 21.5% (+/- 3.5%) in ins/EPO (P < .005). Importantly, signaling intermediaries, previously implicated in induced embryonic/fetal globin gene expression (STAT5, p42/44, and p38), were not differentially activated by SCFAs in eFLCs; but increased bulk histone (H3) acetylation was seen in SCFA-treated eFLCs. SCFAs induce embryonic globin gene expression in eFLCS, which are a useful short-term and physiologic primary cell model of embryonic/fetal globin gene induction during definitive erythropoiesis.

Author information

Author/s: Bhatia, Himanshu (H); Hallock, Jennifer L (JL); Dutta, Amrita (A); Karkashon, Shay (S); Sterner, Lauren S (LS); Miyazaki, Toru (T); Dean, Ann (A); Little, Jane A (JA);

Affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Grants: U24 DK59637 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Blood (Blood), published in United States. (Language: eng)

Reference: 2009-Jun; vol 113 (issue 25) : pp 6440-8

Dates: Created 2009/06/22; Completed 2009/07/20; Revised 2009/08/10;

PMID: 19380871, status: MEDLINE (last retrieved date: 8/21/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Acetylation - drug effects Animals Butyrates - pharmacology Cells, Cultured - cytology; drug effects Erythroid Cells - cytology; drug effects Erythropoiesis - drug effects Fetus - cytology; drug effects Gene Expression Regulation, Developmental - drug effects Gestational Age Humans Liver - cytology; embryology Male

Male Methylmalonyl-CoA Decarboxylase - deficiency; genetics; metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phosphorylation - drug effects Propionates - pharmacology Protein Processing, Post-Translational - drug effects Recombinant Fusion Proteins - biosynthesis; genetics beta-Globins - biosynthesis; genetics gamma-Globins - biosynthesis; genetics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Butyrates (0) ; Propionates (0) ; Recombinant Fusion Proteins (0) ; beta-Globins (0) ; gamma-Globins (0) ; Methylmalonyl-CoA Decarboxylase (EC 4.1.1.41)

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