Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells

Haruhiko Kanasaki, Kohji Fukunaga, Kentaro Takahashi, Kohji Miyazaki, Eishichi Miyamoto

研究成果: Article査読

54 被引用数 (Scopus)

抄録

Bromocriptine, a dopamine D2 receptor agonist, is a therapeutic agent for patients with prolactinoma and hyperprolactinemia. In this study we demonstrated that bromocriptine induced activation of p38 mitogen-activated protein (MAP) kinase, with concomitant induction of apoptosis in rat pituitary adenoma cell line GH3 cells. Treatment of GH3 cells for 48 h with bromocriptine increased the p38 MAP kinase activity up to 3- to 5-fold and simultaneously increased the number of apoptotic cells. Inclusion in the medium of SB212090 or SB203580, specific p38 MAP kinase inhibitors, completely abolished the bromocriptine-induced activation of p38 MAP kinase and significantly reduced the number of apoptotic cells. The bromocriptine- induced p38 MAP kinase activation was not prevented by S(-)-eticropride hydrochloride, a specific D2 receptor antagonist. Treatment with either epidermal growth factor (EGF) or thyrotropin-releasing hormone (TRH), which stimulates p44/42 MAP kinase, rescued cells from the bromocriptine-induced apoptosis, with concomitant inhibition of the bromocriptine-induced p38 MAP kinase activation. These results suggest that bromocriptine induces apoptosis in association with p38 MAP kinase activation, and that the p44/42 MAP kinase signaling through EGF and TRH receptors has an opposing effect on p38 MAP kinase activation as well as on apoptosis induced with bromocriptine in GH3 cells.

本文言語English
ページ(範囲)1486-1494
ページ数9
ジャーナルBiology of Reproduction
62
6
DOI
出版ステータスPublished - 2000
外部発表はい

ASJC Scopus subject areas

  • 生殖医学
  • 細胞生物学

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