Prolonged alkylcatechol‐induced expression of c‐jun proto‐oncogene followed by elevation of NGF mRNA in cultured astroglial cells

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Abstract
We have already shown that alkylcatechol markedly enhances synthesis/secretion of nerve growth factor (NGF) in cultured mouse fibroblasts and astroglial cells through immediate accumulation of NGF mRNA and that the stimulatory effect of alkylcatechol on NGF synthesis/secretion is synergistically enhanced by the coadministration of phorbol 12‐myristate 13‐acetate (PMA). The stimulatory effect on NGF mRNA expression of astroglial cells in culture by 4‐methylcatechol (MC), an alkylcatechol, and/or PMA was blocked by treatment of the cells with cycloheximide, suggesting de novo synthesis of some cellular protein(s) is essential for the observed increase in the NGF mRNA level. The exposure to MC and/or PMA caused a rapid increase in c‐fos mRNA content, which was immediately followed by an increase in c‐jun mRNA, prior to NGF mRNA elevation. The expression of c‐fos mRNA was transiently enhanced in all cases of the treatment with MC and/or PMA. The c‐jun mRNA expression was also observed transiently when the cells were treated with PMA alone, while the expression of c‐jun mRNA was pronounced and long‐lasting after the treatment with MC, which was much further enhanced by the coadministration of PMA. The result that the profile of the change in c‐jun mRNA expression resembled that in NGF mRNA expression suggests that the increase in c‐jun mRNA is responsible for the subsequent increase in NGF mRNA after MC treatment. The cotransfection of mouse astroglial cells with expression plasmids of c‐fos and/or c‐jun and NGF promoter gene showed that simultaneous expression of both c‐fos and c‐jun genes was necessary to enhance NGF promoter activity. These results suggest that alkylcatechol induces NGF mRNA by means of transient induction of c‐fos mRNA and long‐lasting induction of c‐jun mRNA.