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Modulation of glutathione transferase P1–1 activity by retinoic acid in neuroblastoma cells
Author(s) -
Bernardini S.,
Melino G.,
Cortese C.,
Ballerini S.,
AnnicchiaricoPetruzzelli M.,
Bernassola F.,
Corazzari M.,
Federici G.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991201)75:3<375::aid-jcb3>3.0.co;2-i
Subject(s) - retinoic acid , glutathione , gstp1 , glutathione s transferase , microbiology and biotechnology , isozyme , biochemistry , retinoic acid receptor , biology , tretinoin , enzyme , chemistry , gene
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. J. Cell. Biochem. 75:375–381, 1999. © 1999 Wiley‐Liss, Inc.