title: The cytoprotective role of autophagy in puromycin aminonucleoside treated human podocytes.
abstract: Autophagy is a ubiquitous catabolic process involving degradation of damaged organelles and protein aggregates. It shows cytoprotective effects in many cell types and helps to maintain cell homeostasis. In many glomerular diseases, podocyte damage leads to the disruption of the renal filtration barrier and subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces podocyte apoptosis in vitro and in vivo is widely used for studying the pathophysiology of glomerular diseases. It has been shown that PAN induces autophagy in podocytes. However, the relationship between autophagy and apoptosis in PAN treated human podocytes is not known and the role of PAN-induced autophagy in podocyte survival remains unclear. Here we demonstrate that PAN induced autophagy in human podocytes prior to apoptosis which was featured with the activation of mTOR complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3-methyladenine (3-MA) or chloroquine (CQ), podocyte apoptosis increased significantly along with the elevation of active caspase-3. Under such circumstance, the podocyte cytoskeleton was also disrupted. Collectively, our results suggested that the induced autophagy may be an early adaptive cytoprotective mechanism for podocyte survival after PAN treatment.
authors: Department of Health Technology and Informatics, Faculty of Health and Social Science, The Hong Kong Polytechnic University, Hunghom, Hong Kong, China; Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yu-Lin
authors: YL
authors: Kang
authors: Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom.
authors: Moin Ahson
authors: MA
authors: Saleem
authors: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
authors: Kwok Wah
authors: KW
authors: Chan
authors: Department of Health Technology and Informatics, Faculty of Health and Social Science, The Hong Kong Polytechnic University, Hunghom, Hong Kong, China.
authors: Benjamin Yat-Ming
authors: BY
authors: Yung
authors: Department of Health Technology and Informatics, Faculty of Health and Social Science, The Hong Kong Polytechnic University, Hunghom, Hong Kong, China. Electronic address: hthelen@polyu.edu.hk.
authors: Helen Ka-Wai
authors: HK
authors: Law
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006801:Humans; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011692:Puromycin Aminonucleoside / Q000008:administration & dosage*
chemical_list: D011692:Puromycin Aminonucleoside
keywords: Apoptosis; Autophagy; Cytoskeleton; Podocyte; Puromycin aminonucleoside