n-Butyrate induces plasminogen activator inhibitor type 1 messenger RNA in cultured Hep G2 cells

Terry J. Smith, James J. Piscatelli, Valerie Andersen, Hwai Shi Wang, Michael P Lance

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

n-Butyrate, a short-chain aliphatic carboxylic acid with pleiotropic actions, is present at high concentrations in the portal circulation and thus may play an important role in the regulation of specific gene expression in the mammalian liver. We report here that n-butyrate can increase substantially the level of plasminogen activator inhibitor type 1 (PAI-1) messenger RNA (mRNA) in Hep G2 cells, up to eightfold above control cultures. Maximal effects occurred at a concentration of 3 mmol/L n-butyrate and with a treatment period of 8 to 12 hours. Increases in PAI-1 mRNA were accompanied by modest increases (twofold) in the encoded protein as assessed by specific enzyme-linked immunosorbent assay and by [35S]methionine incorporation into immunoprecipitable PAI-1 in the culture medium. Nuclear run-on studies showed that the rate of transcription of the PAI-1 gene did not appear altered by treatment with 3 mmol/L n-butyrate for 6 hours. The increases in steady- state PAI-1 mRNA caused by exposure to n-butyrate can be blocked by cycloheximide. Enhanced stability of mature PAI-1 transcript could not be demonstrated in Hep G2 cells treated with the carboxylic acid. We have reported previously that n-butyrate can reduce the level of β-galactoside α2,6-sialyltransferase expression in Hep G2 cells. That effect was attenuated with inhibitors of protein and RNA synthesis and was mediated at the posttranscriptional level. Thus, n-butyrate can influence the expression of multiple genes in this hepatoblastoma cell through its actions on events that appear to be posttranscriptional. These observations may be relevant to the normal physiology of the mammalian liver because of the high concentrations of n-butyrate and related compounds to which the organ is ordinarily exposed.

Original languageEnglish (US)
Pages (from-to)866-871
Number of pages6
JournalHepatology
Volume23
Issue number4
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Butyrates
Plasminogen Activator Inhibitor 1
Hep G2 Cells
Cultured Cells
Messenger RNA
Carboxylic Acids
Sialyltransferases
Nucleic Acid Synthesis Inhibitors
Hepatoblastoma
Galactosides
Protein Synthesis Inhibitors
Liver
Gene Expression Regulation
Cycloheximide
Methionine
Culture Media
Fatty Acids
Enzyme-Linked Immunosorbent Assay
Gene Expression
Therapeutics

ASJC Scopus subject areas

  • Hepatology

Cite this

n-Butyrate induces plasminogen activator inhibitor type 1 messenger RNA in cultured Hep G2 cells. / Smith, Terry J.; Piscatelli, James J.; Andersen, Valerie; Wang, Hwai Shi; Lance, Michael P.

In: Hepatology, Vol. 23, No. 4, 1996, p. 866-871.

Research output: Contribution to journalArticle

Smith, Terry J. ; Piscatelli, James J. ; Andersen, Valerie ; Wang, Hwai Shi ; Lance, Michael P. / n-Butyrate induces plasminogen activator inhibitor type 1 messenger RNA in cultured Hep G2 cells. In: Hepatology. 1996 ; Vol. 23, No. 4. pp. 866-871.
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abstract = "n-Butyrate, a short-chain aliphatic carboxylic acid with pleiotropic actions, is present at high concentrations in the portal circulation and thus may play an important role in the regulation of specific gene expression in the mammalian liver. We report here that n-butyrate can increase substantially the level of plasminogen activator inhibitor type 1 (PAI-1) messenger RNA (mRNA) in Hep G2 cells, up to eightfold above control cultures. Maximal effects occurred at a concentration of 3 mmol/L n-butyrate and with a treatment period of 8 to 12 hours. Increases in PAI-1 mRNA were accompanied by modest increases (twofold) in the encoded protein as assessed by specific enzyme-linked immunosorbent assay and by [35S]methionine incorporation into immunoprecipitable PAI-1 in the culture medium. Nuclear run-on studies showed that the rate of transcription of the PAI-1 gene did not appear altered by treatment with 3 mmol/L n-butyrate for 6 hours. The increases in steady- state PAI-1 mRNA caused by exposure to n-butyrate can be blocked by cycloheximide. Enhanced stability of mature PAI-1 transcript could not be demonstrated in Hep G2 cells treated with the carboxylic acid. We have reported previously that n-butyrate can reduce the level of β-galactoside α2,6-sialyltransferase expression in Hep G2 cells. That effect was attenuated with inhibitors of protein and RNA synthesis and was mediated at the posttranscriptional level. Thus, n-butyrate can influence the expression of multiple genes in this hepatoblastoma cell through its actions on events that appear to be posttranscriptional. These observations may be relevant to the normal physiology of the mammalian liver because of the high concentrations of n-butyrate and related compounds to which the organ is ordinarily exposed.",
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