著者
茂木 肇 嶋村 雄哉 木村 光利 荻原 政彦 Moteki Hajime / Shimamura Yuya / Kimura Mitsutoshi / Ogihara Masahiko モテキ ハジメ シマムラ ユウヤ キムラ ミツトシ オギハラ マサヒコ
出版者
出版者:Elsevier
雑誌
European Journal of Pharmacology (ISSN:00142999)
巻号頁・発行日
vol.683, no.1, pp.276-284,
被引用文献数
15

We examined the effects of L-ascorbic acid and its analogues onDNA synthesis and cell proliferation. We also investigated the signaltransduction pathways involved in the induction of mitogenesis byL-ascorbic acid and its analogues using primary cultures of adult rathepatocytes. Following a 4-h serum-free cultivation, both L-ascorbic acidand its stable analogue, L-ascorbic acid 2-glucoside, time- anddose-dependently stimulated hepatocyte DNA synthesis and cellproliferation, with EC50 values of 6.46 ? 10-8 M and 3.34 ? 10-8 M,respectively. Dehydroascorbic acid (10-6 M - 10-5 M) weakly stimulatedhepatocyte mitogenesis, whereas isoascorbic acid (10-9 M ? 10-5 M) had noeffect. Hepatocyte mitogenesis induced by L-ascorbic acid or L-ascorbic acid2-glucoside was dose-dependently abolished by treatment with monoclonalantibodies against insulin-like growth factor (IGF)-I receptor, but not bytreatment with monoclonal antibodies against insulin receptor or IGF-IIreceptor. Western blot analysis showed that both L-ascorbic acid andL-ascorbic acid 2-glucoside significantly stimulated IFG-I receptor tyrosinekinase activity within 3 min, and mitogen-activated protein (MAP) kinaseactivity within 5 min. These results demonstrate that both L-ascorbic acidand L-ascorbic acid 2-glucoside induce DNA synthesis and cell proliferationin primary cultures of adult rat hepatocytes by interacting with the IGF-Ireceptor site and by activating the receptor tyrosine kinase/MAP kinasepathway.

言及状況

外部データベース (DOI)

Twitter (2 users, 2 posts, 1 favorites)

こんな論文どうですか? Signal transduction pathway for l-ascorbic acid- and l-ascorbic acid 2-glucoside(茂木 肇ほか), http://t.co/p6ng6YFwDO

収集済み URL リスト