Decreased activity of inducible nitric oxide synthase type 2 and modulation of the expression of glutathione S-transferase α, bcl-2, and metallothioneins during the differentiation of CaCo-2 cells

Françoise Vecchini*, Eric Pringault, Timothy R. Billiar, David A. Geller, Pierrette Hausel, Emanuela Felley-Bosco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Reactive oxygen species modulate the cell growth of a wide variety of mammalian cells. To determine whether oxidative metabolism is altered during the differentiation process, we studied the expression of pro- and antioxidant proteins in proliferating and differentiated CaCo-2 cells, a human colon adenocarcinoma cell line. Nitric oxide synthase type 2 (iNOS) produces nitric oxide (NO). Depending on its rate of synthesis, NO may either promote cellular and DNA damage or reduce the ability of other free radicals to induce cell injury. Using Western and Northern blot analysis and arginine conversion assay, we demonstrate that the expression of iNOS decreases when cells undergo differentiation. This biological event entails a diminished production of NO metabolites and correlates with the loss of activation of soluble guanylate cyclase activity. In differentiated cells, a 2-fold down- regulation of the nuclear factor κB activity was observed, suggesting that nuclear factor κB could be one of the iNOS gene regulatory factors in the CaCo-2 model. In parallel, we studied the expression of other antioxidant proteins including glutathione S-transferase α (GSTα), bcl-2, and the metallothioneins (MTs). We show that the protein levels of GSTα and MT increase during the differentiation of CaCo-2 cells, whereas bcl-2 levels decrease. Our investigation indicates that the expression of iNOS, GSTα, bcl-2, and MT is associated with the enterocytic differentiation. The shift in the expression of specific antioxidant genes during CaCo-2 cell differentiation may occur to avoid alterations in the cell radox potential.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalCell Growth and Differentiation
Volume8
Issue number2
StatePublished - 1997
Externally publishedYes

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