Niemann-Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines.
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.
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Tatsuo
T
Adachi
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Kenichi
K
Ishii
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Yasuhiko
Y
Matsumoto
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Yohei
Y
Hayashi
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Hiroshi
H
Hamamoto
*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Kazuhisa
K
Sekimizu
D017667:Adipocytes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003412:Cricetulus; D006023:Glycoproteins / Q000378:metabolism*; D007313:Insecta; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006023:Glycoproteins; C104585:NPC2 protein, human; D011994:Recombinant Proteins; D014280:Triglycerides; D033921:Vesicular Transport Proteins