Establishment of a Novel Ghrelin-Producing Cell Line

被引:56
作者
Iwakura, Hiroshi [1 ]
Li, Yushu [1 ]
Ariyasu, Hiroyuki [1 ]
Hosoda, Hiroshi [4 ]
Kanamoto, Naotetsu [2 ,3 ]
Bando, Mika [1 ]
Yamada, Go [2 ,3 ]
Hosoda, Kiminori [2 ,3 ]
Nakao, Kazuwa [2 ,3 ]
Kangawa, Kenji [4 ]
Akamizu, Takashi [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Kyoto Univ Hosp, Ghrelin Res Project, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Med, Kyoto Univ Hosp, Translat Res Ctr, Kyoto 6068507, Japan
[3] Kyoto Univ, Grad Sch Med, Kyoto Univ Hosp, Dept Med & Clin Sci, Kyoto 6068507, Japan
[4] Natl Cardiovasc Ctr, Res Inst, Osaka 5658565, Japan
关键词
GROWTH-FACTOR-I; PLASMA GHRELIN; CIRCULATING GHRELIN; MOUSE MODEL; SECRETION; HUMANS; SOMATOSTATIN; HORMONE; INSULIN; STOMACH;
D O I
10.1210/en.2010-0090
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To establish a tool to study ghrelin production and secretion in vitro, we developed a novel ghrelin-producing cell line, MGN3-1( mouse ghrelinoma 3-1) cells from a gastric ghrelin-producing cell tumor derived from ghrelin-promoter Simian virus 40-T-antigen transgenic mice. MGN3-1 cells preserve three essential characteristics required for the in vitro tool for ghrelin research. First, MGN3-1 cells produce a substantial amount of ghrelin at levels approximately 5000 times higher than that observed in TT cells. Second, MGN3-1 cell expressed two key enzymes for acyl modification and maturation of ghrelin, namely ghrelin O-acyltransferase for acylation and prohormone convertase 1/3 for maturation and the physiological acyl modification and maturation of ghrelin were confirmed. Third, MGN3-1 cells retain physiological regulation of ghrelin secretion, at least in regard to the suppression by somatostatin and insulin, which is well established in in vivo studies. Thus, MGN3-1 cells are the first cell line derived from a gastric ghrelin-producing cell preserving secretion of substantial amounts of ghrelin under physiological regulation. This cell line will be a useful tool for both studying the production and secretion of ghrelin and screening of ghrelin-modulating drugs. ( Endocrinology 151: 2940-2945, 2010)
引用
收藏
页码:2940 / 2945
页数:6
相关论文
共 28 条
[1]   Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay [J].
Akamizu, T ;
Shinomiya, T ;
Irako, T ;
Fukunaga, M ;
Nakai, Y ;
Nakai, Y ;
Kangawa, K .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (01) :6-9
[2]   Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans [J].
Ariyasu, H ;
Takaya, K ;
Tagami, T ;
Ogawa, Y ;
Hosoda, K ;
Akamizu, T ;
Suda, M ;
Koh, T ;
Natsui, K ;
Toyooka, S ;
Shirakami, G ;
Usui, T ;
Shimatsu, A ;
Doi, K ;
Hosoda, H ;
Kojima, M ;
Kangawa, K ;
Nakao, K .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (10) :4753-4758
[3]   Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats [J].
Basa, NR ;
Wang, LX ;
Arteaga, JR ;
Heber, D ;
Livingston, EH ;
Taché, Y .
NEUROSCIENCE LETTERS, 2003, 343 (01) :25-28
[4]   Acetylcholine regulates ghrelin secretion in humans [J].
Broglio, F ;
Gottero, C ;
Van Koetsveld, P ;
Prodam, F ;
Destefanis, S ;
Benso, A ;
Gauna, C ;
Hofland, L ;
Arvat, E ;
van der Lely, AJ ;
Ghigo, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (05) :2429-2433
[5]   Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans [J].
Broglio, F ;
Van Koetsveld, P ;
Benso, A ;
Gottero, C ;
Prodam, F ;
Papotti, M ;
Muccioli, G ;
Gauna, C ;
Hofland, L ;
Deghenghi, R ;
Arvat, E ;
van der Lely, AJ ;
Ghigo, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (10) :4829-4832
[6]   A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans [J].
Cummings, DE ;
Purnell, JQ ;
Frayo, RS ;
Schmidova, K ;
Wisse, BE ;
Weigle, DS .
DIABETES, 2001, 50 (08) :1714-1719
[7]   Ghrelin is produced by the human erythroleukemic HEL cell line and involved in an autocrine pathway leading to cell proliferation [J].
De Vriese, C ;
Grégoire, F ;
De Neef, P ;
Robberecht, P ;
Delporte, C .
ENDOCRINOLOGY, 2005, 146 (03) :1514-1522
[8]   Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells [J].
De Vriese, Carine ;
Delporte, Christine .
JOURNAL OF ENDOCRINOLOGY, 2007, 192 (01) :199-205
[9]   Effects of estrogen and recombinant human insulin-like growth factor-I on ghrelin secretion in severe undernutrition [J].
Grinspoon, S ;
Miller, KK ;
Herzog, DB ;
Grieco, KA ;
Klibanski, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (08) :3988-3993
[10]   Ghrelin octanoylation mediated by an orphan lipid transferase [J].
Gutierrez, Jesus A. ;
Solenberg, Patricia J. ;
Perkins, Douglas R. ;
Willency, Jill A. ;
Knierman, Michael D. ;
Jin, Zhaoyan ;
Witcher, Derrick R. ;
Luo, Shuang ;
Onyia, Jude E. ;
Hale, John E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (17) :6320-6325