Niemann-Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines

Tatsuo Adachi, Kenichi Ishii, Yasuhiko Matsumoto, Yohei Hayashi, Hiroshi Hamamoto, Kazuhisa Sekimizu

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)137-147
Number of pages11
JournalBiochemical Journal
Volume459
Issue number1
DOIs
Publication statusPublished - 2014 Apr 1
Externally publishedYes

Keywords

  • Bombyx mori
  • Humoral factor
  • Insect
  • Lipid metabolism
  • Niemann-Pick disease type C2 (NPC2)
  • Triglyceride (triacylglycerol)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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