Induction of arginase II in human Caco-2 tumor cells by cyclic AMP

The objective of this study was to elucidate the mechanism by which cyclic AMP increases arginase activity in cultured human Caco-2 tumor cells. Caco- 2 cells were incubated for 24 h in the presence of 8-bromo cyclic AMP or fo rskolin, and the cells were harvested, lysed, and assayed for total arginas e activity. Both test agents increased arginase activity by twofold, and th is was attributed to the induction of the arginase II isoform, Both arginas e II mRNA and protein showed increased expression in response to 8-bromo cy clic AMP and forskolin, and these effects were inhibited by H-89 (protein k inase A inhibitor), enhanced by okadaic acid (phosphatase inhibitor), and e nhanced by 1-methyl-3-isobutylxanthine (cyclic nucleotide phosphodiesterase inhibitor). Cyclic GMP did not appear to be involved in arginase II induct ion, These observations indicate that cyclic AMP stimulates arginase II gen e expression by mechanisms involving activation of protein kinase A and con sequent activation of appropriate transcription factors. (C) 2000 Academic Press.