1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis

• Published in: Journal of neuroscience research Vol. 28; no. 1; p. 110
• Main Authors: Wion, D, MacGrogan, D, Neveu, I, Jehan, F, Houlgatte, R, Brachet, P
• Format: Journal Article
• Language: English
• Published: United States 01.01.1991
• Subjects: Animals; Calcitriol - pharmacology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Gene Expression Regulation - drug effects; L Cells (Cell Line) - drug effects; L Cells (Cell Line) - metabolism; Mice; Nerve Growth Factors - biosynthesis; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Proto-Oncogenes - drug effects; Stimulation, Chemical; Transcription Factors - biosynthesis; Transcription Factors - genetics
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490280111

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), a metabolically active form of vitamin D, is shown to increase in a dose-dependent manner the cellular pool of NGF mRNA in murine L-929 fibroblasts cultured in a serum-free medium. This effect can be detected as early as 3 hours after 1,25-(OH)2D3 addition and persists for at least 28 hours. It is accompanied by an enhancement of the amount of NGF protein secreted in the culture medium. Since the proto-oncogene c-fos appears involved in the regulation of the NGF gene (Mocchetti et al.: Proceedings of the National Academy of Sciences of the United States of America 86: 3871-895, 1989; Hengerer et al: Proceedings of the National Academy of Sciences of the United States of America 87:3899-3903, 1990), the effect of 1,25-(OH)2D3 on c-fos expression was analysed and compared to that elicited by other inducers of the NGF gene, serum (Wion et al: FEBS Letters 189:37-41, 1985) and phorbol 12-myristate 13-acetate (PMA) (Wion et al: FEBS Letters 262:42-44, 1990). Addition of serum or PMA to L-929 cells was rapidly followed by a transient activation of the c-fos gene. In contrast, c-fos transcripts remained undetected in the presence of 1,25-(OH)2D3. The failure to find any evidence of c-fos expression suggests that 1,25-(OH)2D3 could enhance the pool of NGF mRNA by a mechanism independent of the c-fos pathway.