Heat shock protein 72 protects kidney proximal tubule cells from injury induced by triptolide by means of activation of the MEK/ERK pathway.
Triptolide, which has been used to treat inflammatory diseases, has also been reported to inhibit proliferation of cancer cells. However, it can cause severe nephrotoxicity, limiting its clinical use. Here, nephrotoxicity of triptolide was observed in vivo and in vitro. Heat shock protein 72 (HSP72) was upregulated during kidney injury in rats. HSP72 partially protected human kidney proximal tubule cell lines HK-2 and HKC from triptolide-induced injury. Phospho-Raf, phospho-MEK and phospho-ERK were elevated in HK-2 cells that overexpressed HSP72 after either heat shock or triptolide treatment, and downregulated when HSP72 was repressed by siRNA. The participation of the MEK/ERK1/2 pathway was confirmed by exposure of the cells to the MEK inhibitor U0126. Collectively, our results suggested that HSP72 plays a protective role by means of the MEK/ERK pathway, against triptolide-induced kidney injury.
Wang
Zhipeng
Z
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. wangzhipeng7763@yahoo.com.cn
Jin
Haifeng
H
Li
Chen
C
Hou
Ying
Y
Mei
Qibing
Q
Fan
Daiming
D
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000378:metabolism / Q000633:toxicity*; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010616:Phenanthrenes / Q000378:metabolism / Q000633:toxicity*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism
D001786:Blood Glucose; D004224:Diterpenes; D004852:Epoxy Compounds; D050884:HSP72 Heat-Shock Proteins; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; C001899:triptolide; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D005947:Glucose