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Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy
Author(s) -
Lim Sun Woo,
Doh Kyoung Chan,
Jin Long,
Jin Jian,
Piao Shang Guo,
Heo Seong Beom,
Chung Byung Ha,
Yang Chul Woo
Publication year - 2014
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12273
Subject(s) - autophagy , medicine , ginseng , sequestosome 1 , pi3k/akt/mtor pathway , pharmacology , apoptosis , atg12 , autophagosome , vacuole , hmgb1 , microbiology and biotechnology , chemistry , biology , receptor , biochemistry , pathology , atg5 , alternative medicine , cytoplasm
Aims Chronic cyclosporine ( CsA ) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy. Methods Mice were treated with CsA (30 mg/kg) with or without K orean red ginseng ( KRG ) extract (0.2, 0.4 g/kg) for 4 weeks. The effect of KRG on CsA ‐induced autophagosome formation was measured using phospholipid‐conjugated form of LC 3‐ II , beclin‐1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC 3‐ II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC 3‐ II and active caspase‐3 was performed. Multiple autophagy pathways were also examined. Results KRG co‐treatment significantly decreased the expression of LC 3‐ II , beclin‐1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA ‐induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC 3‐ II and with each other. KRG treatment simultaneously reduced the expression of both active caspase‐3 and LC 3‐ II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT / mTOR , which is a pathway that inhibits autophagy, and reduced AMPK expression. Conclusion Ginseng treatment attenuated CsA ‐induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA ‐induced autophagic cell death.