Butyrate synchronization of hepatocytes: Modulation of cycling and cell cycle regulated gene expression

Sanjeev Gupta, Gianfranco Alpini, Ravikumar P. Wmuru, Ethel Hurston, David A. Shafritz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

To develop a model for studies of liver growth control, we characterized cell cycle synchronization of liver-derived cells with sodium butyrate. Exposure of cultured HTC (rat hepatoma) cells to 5 mM butyrate arrested cell growth in a reversible manner. Flow cytometric analysis revealed that butyrate-treated HTC cells were restricted in G0/G1, as well as S/G2M phases. After release from butyrate arrest, HTC cells underwent synchronous cycles of DNA synthesis and transited through S phase. Inhibition of cell growth by butyrate was associated with a complex pattern of cell cycle regulated gene expression, including a decoupling of c-fos and c-jun gene expression. Transcription of c-fos, as well as c-jun increased with butyrate arrest, whereas steady rate mRNA levels of c-jun only were increased, suggesting additional regulation of c-fos. In addition, butyrate-arrested cells exhibited a transcriptionally determined accumulation of H3 histone, C-Ha-ras and ornithine decarboxylase mRNAs, suggesting that cell cycle-related check points following the onset of S phase were modulated. An increase in c-myc mRNA levels in butyrate-arrested cells was post-transcriptionally regulated. After release from butyrate-arrest, the abundance of immediate early, as well as S phase regulated, gene expression changed coordinately with S phase cell transitions. Thus, exposure of HTC cells to butyrate modulates cell cycle regulated gene expression, inhibits cycling, and results in accumulation of cells in specific compartments. Synchronization of liver cells with butyrate should, therefore, provide a useful model for defining cell cycle-related events in response to various mitogenic stimuli.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalGrowth Factors
Volume10
Issue number3
DOIs
StatePublished - 1994

Fingerprint

cdc Genes
Butyrates
Gene expression
Hepatocytes
Synchronization
Cells
Modulation
Gene Expression
S Phase
Liver
Cell growth
Messenger RNA
jun Genes
Cell Cycle
Growth
Ornithine Decarboxylase
Butyric Acid
Transcription
Histones
Phase Transition

Keywords

  • Butyrate
  • Cell cycle
  • Gene expression
  • Hepatocyte
  • Protooncogenes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Butyrate synchronization of hepatocytes : Modulation of cycling and cell cycle regulated gene expression. / Gupta, Sanjeev; Alpini, Gianfranco; Wmuru, Ravikumar P.; Hurston, Ethel; Shafritz, David A.

In: Growth Factors, Vol. 10, No. 3, 1994, p. 171-180.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Alpini, Gianfranco ; Wmuru, Ravikumar P. ; Hurston, Ethel ; Shafritz, David A. / Butyrate synchronization of hepatocytes : Modulation of cycling and cell cycle regulated gene expression. In: Growth Factors. 1994 ; Vol. 10, No. 3. pp. 171-180.
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