Trehalose, an mTOR independent autophagy inducer, alleviates human podocyte injury after puromycin aminonucleoside treatment

Yu-Lin Kang, Moin Ahson Saleem, Kwok Wah Chan, Benjamin Yat-Ming Yung, Helen Ka-Wai Law

Research output: Contribution to journalArticle (Academic Journal)

29 Citations (Scopus)

Abstract

Glomerular diseases are commonly characterized by podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine podocyte recovery. It was shown that trehalose induced podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human podocytes and showed cytoprotective effects in PAN-treated podocytes.

Original languageEnglish
Pages (from-to)e113520
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 2014

Keywords

  • Actin Cytoskeleton
  • Antibiotics, Antineoplastic
  • Apoptosis
  • Autophagy
  • Blotting, Western
  • Cell Line
  • Cell Movement
  • Humans
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins
  • Nephrosis, Lipoid
  • Podocytes
  • Puromycin Aminonucleoside
  • Reactive Oxygen Species
  • TOR Serine-Threonine Kinases
  • Trehalose
  • Journal Article
  • Research Support, Non-U.S. Gov't

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