title: Puerarin protects against cadmium-induced proximal tubular cell apoptosis by restoring mitochondrial function.
abstract: Puerarin (PU) is a potent free radical scavenger with a protective effect in nephrotoxin-mediated oxidative damage. Here, we show a novel molecular mechanism by which PU exerts its anti-apoptotic effects in cadmium (Cd)-exposed primary rat proximal tubular (rPT) cells. Morphological assessment and flow cytometric analysis revealed that PU significantly decreased Cd-induced apoptotic cell death of rPT cells. Administration of PU protected cells against Cd-induced depletion of mitochondrial membrane potential (ΔΨm) and lipid peroxidation. Cd-mediated mitochondrial permeability transition pore (MPTP) opening, disruption of mitochondrial ultrastructure, mitochondrial cytochrome c (cyt-c) release, caspase-3 activation and subsequently poly ADP-ribose polymerase (PARP) cleavage could be effectively blocked by the addition of PU. Moreover, up-regulation of Bcl-2 and down-regulation of Bax and hence increased Bcl-2/Bax ratio were observed with the PU administration. In addition, PU reversed Cd-induced ATP depletion by restoring ΔΨm to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU inhibited Cd-induced apoptosis in rPT cells by ameliorating the mitochondrial dysfunction.
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
authors.forename: Xiang-Bin
authors.initials: XB
authors.lastname: Song
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an 271018, People's Republic of China. Electronic address: wanglin2013@sdau.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D042541:Intracellular Space / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D033741:Adenine Nucleotide Translocator 1; D007529:Isoflavones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D002104:Cadmium; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C033607:puerarin
keywords: Apoptosis; Cadmium; Mitochondria; Primary cell culture; Proximal tubular cells; Puerarin