TY - JOUR
T1 - n-Butyrate induces plasminogen activator inhibitor type 1 messenger RNA in cultured Hep G2 cells
AU - Smith, Terry J.
AU - Piscatelli, James J.
AU - Andersen, Valerie
AU - Wang, Hwai Shi
AU - Lance, Peter
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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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U2 - 10.1053/jhep.1996.v23.pm0008666343
DO - 10.1053/jhep.1996.v23.pm0008666343
M3 - Article
C2 - 8666343
SN - 0270-9139
VL - 23
SP - 866
EP - 871
JO - Hepatology
JF - Hepatology
IS - 4
ER -