Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation

Michael S. Boosalis, Ram Bandyopadhyay, Emery H. Bresnick, Betty Sue Pace, Karyn Van Demark, Baohua Zhang, Douglas V. Faller, Susan P. Perrine

Research output: Contribution to journalArticle

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Abstract

Current chemotherapeutic and butyrate therapeutics that induce fetal hemoglobin expression generally also suppress erythropoiesis, limiting the production of cells containing fetal hemoglobin (F cells). Recently, selected short-chain fatty acid derivatives (SCFADs) were identified that induce endogenous γ-globin expression in K562 cells and human burst-forming units-erythroid and that increase proliferation of human erythroid progenitors and a multilineage interleukin-3-dependent hematopoietic cell line. In this report, γ-globin inducibility by these SCFADs was further demonstrated in mice transgenic for the locus control region and the entire β-globin gene locus in a yeast artificial chromosome and in 2 globin promoter-reporter assays. Conditioned media experiments strongly suggest that their proliferative activity is a direct effect of the test compounds. Investigation of potential mechanisms of action of these SCFADs demonstrates that these compounds induce prolonged expression of the growth-promoting genes c-myb and c-myc. Both butyrate and specific growth-stimulatory SCFADs induced prolonged signal transducer and activator of transcription (STAT)-5 phosphorylation and activation, and c-cis expression, persisting for more than 120 minutes, whereas with IL-3 alone phosphorylation disappeared within minutes. In contrast to butyrate treatment, the growth-stimulating SCFADs did not result in bulk histone H4 hyperacetylation or induction of p21Waf/Cip, which mediates the suppression of cellular growth by butyrate. These findings suggest that the absence of bulk histone hyperacetylation and p21 induction, but prolonged induction of cis, myb, myc, and STAT-5 activation, contribute to the cellular proliferation induced by selected SCFADs.

Original languageEnglish (US)
Pages (from-to)3259-3267
Number of pages9
JournalBlood
Volume97
Issue number10
DOIs
StatePublished - May 15 2001

Fingerprint

STAT5 Transcription Factor
Volatile Fatty Acids
Cell proliferation
Transcriptional Activation
Globins
Butyrates
Chemical activation
Cell Proliferation
Derivatives
Fetal Hemoglobin
Phosphorylation
Interleukin-3
Growth
Histones
Genes
myb Genes
Locus Control Region
Yeast Artificial Chromosomes
Erythroid Precursor Cells
Chromosomes, Human, Pair 2

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Boosalis, M. S., Bandyopadhyay, R., Bresnick, E. H., Pace, B. S., Van Demark, K., Zhang, B., ... Perrine, S. P. (2001). Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. Blood, 97(10), 3259-3267. https://doi.org/10.1182/blood.V97.10.3259

Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. / Boosalis, Michael S.; Bandyopadhyay, Ram; Bresnick, Emery H.; Pace, Betty Sue; Van Demark, Karyn; Zhang, Baohua; Faller, Douglas V.; Perrine, Susan P.

In: Blood, Vol. 97, No. 10, 15.05.2001, p. 3259-3267.

Research output: Contribution to journalArticle

Boosalis, MS, Bandyopadhyay, R, Bresnick, EH, Pace, BS, Van Demark, K, Zhang, B, Faller, DV & Perrine, SP 2001, 'Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation', Blood, vol. 97, no. 10, pp. 3259-3267. https://doi.org/10.1182/blood.V97.10.3259
Boosalis MS, Bandyopadhyay R, Bresnick EH, Pace BS, Van Demark K, Zhang B et al. Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. Blood. 2001 May 15;97(10):3259-3267. https://doi.org/10.1182/blood.V97.10.3259
Boosalis, Michael S. ; Bandyopadhyay, Ram ; Bresnick, Emery H. ; Pace, Betty Sue ; Van Demark, Karyn ; Zhang, Baohua ; Faller, Douglas V. ; Perrine, Susan P. / Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. In: Blood. 2001 ; Vol. 97, No. 10. pp. 3259-3267.
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