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Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin\u2010induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin\u2010induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule\u2010associated protein 1A\/1B\u2010light chain 3 (LC3) BII\/I expression and autophagosome formation. Consistently, in cisplatin\u2010injured renal tubular cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    , lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK\u2010\u03b1 phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy\u2010related molecules, like mammalian target of rapamycin and LC3BII\/I. AMPK\u2010\u03b1 activation is likely required for lithium\u2010induced tubular cell autophagy and protection in cisplatin\u2010induced AKI because blockade of AMPK\u2010\u03b1 phosphorylation by compound C markedly abrogated lithium\u2010induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin\u2010induced AKI by enhancing autophagy\n                    <jats:italic>via<\/jats:italic>\n                    AMPK\u2010\u03b1 activation.\u2014Bao, H., Zhang, Q., Liu, X., Song, Y., Li, X., Wang, Z., Li, C., Peng, A., Gong, R. Lithium targeting of AMPK protects against cisplatin\u2010induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells. FASEB J. 33, 14370\u201014381 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901712r","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T18:14:45Z","timestamp":1572372885000},"page":"14370-14381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Lithium targeting of AMPK protects against cisplatin\u2010induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Hui","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Nephrology Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai China"},{"name":"Center for Nephrology and Clinical Metabolomics, Tongji University School of 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