論文

査読有り 国際誌
2020年4月17日

A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway.

The Journal of biological chemistry
  • Yuichi Abe
  • Masanori Honsho
  • Ryoko Kawaguchi
  • Takashi Matsuzaki
  • Yayoi Ichiki
  • Masashi Fujitani
  • Kazushirou Fujiwara
  • Masaaki Hirokane
  • Masahide Oku
  • Yasuyoshi Sakai
  • Toshihide Yamashita
  • Yukio Fujiki
  • 全て表示

295
16
開始ページ
5321
終了ページ
5334
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.RA119.011989

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

リンク情報
DOI
https://doi.org/10.1074/jbc.RA119.011989
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32165495
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170515
ID情報
  • DOI : 10.1074/jbc.RA119.011989
  • PubMed ID : 32165495
  • PubMed Central 記事ID : PMC7170515

エクスポート
BibTeX RIS