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Title: Trehalose, a mTOR independent autophagy inducer, alleviates human podocyte injury after puromycin aminonucleoside treatment
Authors: Kang, YL
Saleem, M
Chan, KW
Yung, BY 
Law, HKW 
Issue Date: 2014
Publisher: Karger
Source: Nephron clinical practice, 2014, v. 126, no. 4, 12, p. 165 (Abstracts) How to cite?
Journal: Nephron clinical practice 
Abstract: Introduction: Glomerular diseases are commonly character-ized by podocyte injury including apoptosis, detachment and actin cytoskeleton rearrangement. However, the strategies for prevent-ing podocyte damage remains insufficient. Recently, autophagy has been regarded as a vital cytoprotective mechanism for podo-cyte homeostasis. Trehalose, a natural disaccharide, has shown to be a mTOR independent autophagy inducer. Its cytoprotective role has been demonstrated in neurodegenerative diseases. How-ever, it remains unknown whether it may alleviate podocyte injury. In this study, investigated the effect of trehalose in puromycin ami-nonucleoside-treated podocytes which mimics minimal change nephrotic syndrome.
Methods: Human conditional immortalized podocytes were treated with PAN±Trehalose. Then autophagy was being investi-gated by immunofluorecence staining for LC3 puncta and western blotting for LC3, mTOR and its substrates. Podocyte apoptosis and necrosis was evaluated by flow cytometry and by measuring lactate dehydrogenase (LDH) activity respectively. We also performed the podocyte migration and adhesion assays to evaluate podocyte re-covery. Furthermore, for studying the mechanism of trehalose in-duced autophagy, chloroquine (CQ) and wortmannin (WT) were used to inhibit autophagy.
Results: Trehalose induced podocyte autophagy in an mTOR independent manner and podocyte apoptosis was significantly de-creased after trehalose treatment. Moreover, the inhibition of tre-halose-triggered autophagy abolished its protective effect. Addi-tionally, the disrupted actin cytoskeleton of podocytes was also partially reversed by trehalose, accompanying with the decreased mobility and less lamellipodias.
Conclusions: These results suggest that trehalose induced au-tophagy in human podocytes and demonstrated cytoprotective ef-fects in alleviating podocyte injury. Further investigation is war-ranted to determine whether it may be a therapeutic candidate for glomerular diseases.
Description: 10th International Podocyte Conference, Freiburg, Germany, 4-6 June 2014
EISSN: 1660-2110
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