Modulation of glutathione transferase P1-1 activity by retinoic acid in neuroblastoma cells

Sergio Bernardini, G. Melino, C. Cortese, S. Ballerini, M. Annicchiarico-Petruzzelli, F. Bernassola, M. Corazzari, G. Federici

Research output: Contribution to journalArticle

Abstract

The ability of retinoic acid to modulate glutathione S-transferase P1-1 (GSTP1-1) activity has important implications both for cancer prevention and for anticancer therapy. We investigated GSTP1-1 expression and activity in the human neuroblastoma cell line SK-N-BE(2) (genotype A*/B*) under basal conditions and during 48-h incubation with 0.1 μM all-trans-retinoic acid. The steady-state levels of glutathione transferase P1-1 mRNA and protein during 48-h incubation with all-trans-retinoic acid did not increase substantially, but we detected a significant reduction of GSTP1-1 specific activity. This reduction in enzymatic activity could not be ascribed to a differential action of retinoic acid on the gene variants A* and B*; indeed, the two GSTP1-1 isoforms have different affinities toward 1-chloro- 2,4-dinitrobenzene (CDNB), while we found a substantial invariance of the K(m) (CDNB) in the cytosol during retinoid treatment. A modulatory effect of retinoic acid on other enzymes involved in glutathione transferase P1-1 metabolism, such as the retinoic acid-induced tissue trans-glutaminase, might be hypothesized, as well as a direct inactivation of GSTP1-1 by the oxidative stress that characterizes the early phases of apoptosis.

Original languageEnglish
Pages (from-to)375-381
Number of pages7
JournalJournal of Cellular Biochemistry
Volume75
Issue number3
DOIs
Publication statusPublished - Dec 1 1999

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Keywords

  • Glutathione transferase P1-1
  • Neuroblastoma
  • Retinoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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