title: Restoration of autophagy by puerarin in lead-exposed primary rat proximal tubular cells via regulating AMPK-mTOR signaling.
abstract: Previous study has demonstrated that puerarin (PU) exerts nephroprotective effect against Pb-induced cytotoxicity in primary rat proximal tubular (rPT) cells. Autophagy can protect cells from various cytotoxic stimuli, but its role in the process of PU against Pb-induced nephrotoxicity is still unknown. This study aims to investigate whether PU can alleviate Pb-induced renal damage by recovering autophagy. Data showed that Pb inhibited the autophagic flux, as evidenced by the accumulation of LC3-II and p62 as well as the confocal microscopy analysis of GFP-LC3 puncta and punctate spots of monodansylcadaverine staining, whereas coadministration of PU could restore Pb-induced autophagy inhibition. Moreover, PU dramatically enhanced the phosphorylation of 5'AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins p70S6 kinase (p70S6K) and 4E-binding protein 1 (4E-BP1) in Pb-exposed rPT cells. Collectively, these evidence suggested that PU restored the impaired autophagic flux in Pb-treated rPT cells partly by activating autophagy via AMPK/mTOR-mediated signaling pathway.
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, People's Republic of China.
authors.forename: Xiangbin
authors.initials: X
authors.lastname: Song
authors.affiliation: Laboratory Animal Center of Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China.
authors.forename: Zifa
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, People's Republic of China.
authors.forename: Zhenyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones / Q000008:administration & dosage*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D007854:Lead / Q000633:toxicity; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones; D010750:Phosphoproteins; D007854:Lead; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C033607:puerarin
keywords: 5ʹAMP-activated protein kinase (AMPK); Puerarin; autophagy; lead; mammalian target of rapamycin (mTOR)