Alleviation of Lead-Induced Apoptosis by Puerarin via Inhibiting Mitochondrial Permeability Transition Pore Opening in Primary Cultures of Rat Proximal Tubular Cells.
Previous study has demonstrated that mitochondrial-dependent apoptotic pathway is involved in the nephroprotective effect of puerarin (PU) against lead-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. To further clarify how PU exerts its antiapoptotic effects, this study was designed to investigate the role of mitochondrial permeability transition (MPT) and subsequent apoptotic events in the process of PU against Pb-induced cytotoxicity in rPT cells. The results showed that Pb-mediated mitochondrial permeability transition pore (MPTP) opening together with mitochondrial cytochrome c release, activations of caspase-9 and caspase-3, and subsequent poly-ADP-ribose polymerase (PARP) cleavage can be effectively blocked by the addition of PU. Simultaneously, upregulation and downregulation of Bcl-2 and Bax with increased Bcl-2/Bax ratio due to PU administration further alleviated Pb-induced mitochondrial apoptosis. Moreover, PU can reverse Pb-induced ATP depletion by restoring mitochondrial fragmentation to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU produced a significant protection against Pb-induced mitochondrial apoptosis in rPT cells by inhibiting MPTP opening to ameliorate the mitochondrial dysfunction.
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an, 271018, China.
Zhong-Kun
ZK
Wang
Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611130, China.
Xue-Lei
XL
Zhou
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an, 271018, China.
Xiang-Bin
XB
Song
Institute of Pathogen Biology, Taishan Medical College, East Road of Yingsheng No.2, Tai'an, 271000, China.
Dong-Ming
DM
Zhuang
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an, 271018, China.
Zhen-Yong
ZY
Wang
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an, 271018, China.
Du-Bao
DB
Yang
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Daizong Road No. 61, Tai'an, 271018, China. wanglin2013@sdau.edu.cn.
Lin
L
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D007529:Isoflavones / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D061251:Primary Cell Culture; D051381:Rats
D007529:Isoflavones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D007854:Lead; C033607:puerarin
Apoptosis; Lead; Mitochondria; Mitochondrial permeability transition; Proximal tubular cells; Puerarin