Biphasic effect of IL-1β on the activity of argininosuccinate synthetase in Caco-2 cells. Involvement of nitric oxide production

• Published in: Biochimie Vol. 88; no. 6; pp. 607 - 612
• Main Authors: Brasse-Lagnel, Carole, Lavoinne, Alain, Fairand, Alain, Vavasseur, Karine, Deniel, Nicolas, Husson, Annie
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.06.2006
• Subjects: Argininosuccinate synthetase; Caco-2 cells; Interleukin-1β; Nitric oxide; ASS; DMEM; Argininosuccinate synthetase; Caco-2 cells; NOS; Interleukin-1β; Nitric oxide; IL-1β; SNAP; INF-γ; l-NMMA
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2005.11.005

The expression of the argininosuccinate synthetase gene (ASS), the limiting enzyme of arginine synthesis, was previously shown to be rapidly induced by a short-term (4 h) exposure to IL-1β in Caco-2 cells [Biochimie, 2005, 403–409]. The present report shows that, by contrast, a long-term (24 h) exposure to IL-1β inhibited the ASS activity despite an increase in both specific mRNA level and protein amount, demonstrating a post-translational effect. Concerning the mechanism involved, we demonstrate that the inhibiting effect is linked to the production of nitric oxide (NO) induced by IL-1β. Indeed, the inhibiting effect of IL-1β was totally blocked in the presence of l-NMMA, an inhibitor of the inducible nitric oxide synthase, or by culturing the cells in an arginine-deprived medium. Moreover, a decrease in the ASS activity was induced by culturing the cells in the presence of SNAP, a NO donor. Conversely, blocking the action of NO by antioxidant agents, the stimulatory effect of IL-1β on ASS activity was restored, as measured at 24 h. Finally, such an inhibiting effect of NO on ASS activity may be related, at least in part, to S-nitrosylation of the protein. The physiological relevance of the antagonistic effects of IL-1β and NO on ASS is discussed.