Chronic Cyclosporine Nephropathy Is Characterized by Excessive Autophagosome Formation and Decreased Autophagic Clearance

• DOI: 10.1097/tp.0b013e31825ace5c
• Publication Date: 2012-07-11T10:36:18Z
• Authors: Sun Woo Lim; Bok Jin Hyoung; Shang Guo Piao; Kyoung Chan Doh; Byung Ha Chung; Chul Woo Yang
• Keywords: Sequestosome 1; BECN1; Deoxyguanosine

Background The study was performed to investigate the influence of cyclosporine A (CsA)–induced renal injury on autophagy in an experimental model chronic CsA nephropathy. Methods Three dosages (7.5, 15, and 30 mg/kg/day) were administered mice for 4 weeks. formation autophagosomes measured with microtubule-associated protein 1 light chain 3 phospholipid-conjugated form (LC3-II) beclin-1, ability autophagic clearance examined sequestosome-1 (p62). Autophagic vacuoles visualized counted using electron microscopy. Double immunolabeling LC3-II active caspase-3 evaluate association between apoptosis. Oxidative stress evaluated by measuring urinary 8-hydroxy-2′-deoxyguanosine excretion, demonstrating oxidative DNA damage. Antioxidative drugs, pravastatin N-acetylcysteine, used role CsA-induced autophagy. Results treatment increased expressions beclin-1 kidney a dose-dependent manner. number p62-positive cells also significantly dose–dependent Electron microscopy revealed excessive group compared vehicle group. Expression manner colocalized injured area CsA-treated kidneys. Concurrent or N-acetylcysteine reduced excretion subsequently decreased expression Conclusions Chronic nephropathy is state clearance. may play importation induction