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

✍ Scribed by S. Bernardini; G. Melino; C. Cortese; S. Ballerini; M. Annicchiarico-Petruzzelli; F. Bernassola; M. Corazzari; G. Federici

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 151 KB
• Volume: 75
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19991201)75:3<375::aid-jcb3>3.0.co;2-i

✦ Synopsis

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-2,4dinitrobenzene (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.