Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation
10.1182/blood.v97.10.3259
Crossref journal-article
American Society of Hematology
Blood (234)
Abstract

AbstractCurrent 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 andc-myc. Both butyrate and specific growth-stimulatory SCFADs induced prolonged signal transducer and activator of transcription (STAT)-5 phosphorylation and activation, and c-cisexpression, 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.

Bibliography

Boosalis, M. S., Bandyopadhyay, R., Bresnick, E. H., Pace, B. S., Van DeMark, K., Zhang, B., Faller, D. V., & Perrine, S. P. (2001). Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. Blood, 97(10), 3259–3267.

Authors 8
  1. Michael S. Boosalis (first)
  2. Ram Bandyopadhyay (additional)
  3. Emery H. Bresnick (additional)
  4. Betty S. Pace (additional)
  5. Karyn Van DeMark (additional)
  6. Baohua Zhang (additional)
  7. Douglas V. Faller (additional)
  8. Susan P. Perrine (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 8:46 a.m.)
Deposited 1 year, 8 months ago (Jan. 6, 2024, 1:42 a.m.)
Indexed 11 months, 3 weeks ago (Sept. 14, 2024, 11:16 a.m.)
Issued 24 years, 3 months ago (May 15, 2001)
Published 24 years, 3 months ago (May 15, 2001)
Published Print 24 years, 3 months ago (May 15, 2001)
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@article{Boosalis_2001, title={Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation}, volume={97}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v97.10.3259}, DOI={10.1182/blood.v97.10.3259}, number={10}, journal={Blood}, publisher={American Society of Hematology}, author={Boosalis, Michael S. and Bandyopadhyay, Ram and Bresnick, Emery H. and Pace, Betty S. and Van DeMark, Karyn and Zhang, Baohua and Faller, Douglas V. and Perrine, Susan P.}, year={2001}, month=may, pages={3259–3267} }