Silkworm haemolymph induced both the cessation of growth and an increase in triglyceride (triacylglycerol) storage in BmN4 cells. We purified the growth inhibitory factor from the silkworm haemolymph and identified this protein as the Bombyx mori PP (promoting protein), an orthologue of NPC2 (Niemann–Pick disease type C2) protein. Recombinant silkworm NPC2 inhibited cellular proliferation and increased triglyceride accumulation in BmN4 cells. Injection of either the recombinant protein or antiserum of NPC2 into living silkworms increased or decreased respectively triglyceride levels in the fat body. A mutation that depletes the cholesterol-binding capacity did not abolish the activity of NPC2. We further revealed that NPC2 induced the phosphorylation of AMPK (AMP-activated protein kinase) and that an AMPK inhibitor suppressed NPC2-dependent triglyceride accumulation. These findings suggest that NPC2 induces triglyceride accumulation via the activation of AMPK independently of its cholesterol-binding capacity in the silkworm.
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Research Article|
March 14 2014
Niemann–Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines
Tatsuo Adachi;
Tatsuo Adachi
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
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Kenichi Ishii;
Kenichi Ishii
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
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Yasuhiko Matsumoto;
Yasuhiko Matsumoto
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
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Yohei Hayashi;
Yohei Hayashi
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
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Hiroshi Hamamoto;
Hiroshi Hamamoto
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
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Kazuhisa Sekimizu
Kazuhisa Sekimizu
1
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
1To whom correspondence should be addressed (email sekimizu@mol.f.u-tokyo.ac.jp).
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Publisher: Portland Press Ltd
Received:
July 01 2013
Revision Received:
January 10 2014
Accepted:
January 20 2014
Accepted Manuscript online:
January 20 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (1): 137–147.
Article history
Received:
July 01 2013
Revision Received:
January 10 2014
Accepted:
January 20 2014
Accepted Manuscript online:
January 20 2014
Citation
Tatsuo Adachi, Kenichi Ishii, Yasuhiko Matsumoto, Yohei Hayashi, Hiroshi Hamamoto, Kazuhisa Sekimizu; Niemann–Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines. Biochem J 1 April 2014; 459 (1): 137–147. doi: https://doi.org/10.1042/BJ20130876
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