Posttranscriptional regulation of MRP/GS-X pump and γ-glutamylcysteine synthetase expression by 1 -(4-amino-2-methyl-5-pyrimidinyl) methyl-3(2-chloroethyl)-3-nitrosourea and by cycloheximide in human glioma cells

Akira Gomi, Toshio Masuzawa, Toshihisa Ishikawa, M. Tien Kuo

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Treatment of human glioma A172 cells with 1-(4-amino-2-methyl-5 -pyrimidinyl)methyl-3- (2-chloroethy-3-nitrosourea (ACNU) for 2 to 4 hr resulted in a 2- to 3-fold increase in steady-state levels of multidrug resistance-associated protein (MRP) and γ-glutamylcysteine synthetase (γ-GCS) mRNA. Nuclear run-on assays revealed a less than 0.5-fold increase in transcription rates of these genes under the same treatment conditions, suggesting that posttranscriptional regulation plays an important role for the increased mRNA levels. In the absence of ACNU, rates of MRP and γ-GCS mRNA degradation were similar in A172 cells as determined by incubating cells with the RNase inhibitor, Actinomycin D. ACNU treatments resulted in increased MRP mRNA stability. Induction of MRP and γ-GCS mRNA by ACNU apparently did not require de novo protein synthesis as determined by the use of protein synthesis inhibitor cycloheximide (CHX). However, CHX alone could induce accumulation of γ-GCS mRNA, also by posttranscriptional mechanism. Taken together, these results demonstrate that (i) posttranscriptional regulation is primarily involved in the induction of MRP and γ-GCS expression by ACNU and CHX in human glioma cells; and (ii) despite the fact that these two genes have been reported to be frequently co-expressed, their responses to the treatments of RNA and protein synthesis inhibitors are not the same.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalBiochemical and biophysical research communications
Volume239
Issue number1
DOIs
StatePublished - Oct 9 1997

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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