Increased expression of heat shock protein 72 protects renal proximal tubular cells from gentamicin-induced injury.
The nephrotoxicity of gentamicin (GM) has been widely recognized. Heat shock protein 72 (HSP72) has been reported to be a cytoprotectant. However, its cytoprotective effect against GM induced kidney injury has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on GM-induced nephrotoxicity in vitro. Human Kidney tubular cell line, HK-2 cells were divided into four groups: control group, GM group (cells incubated with GM only), heat shock (HS) group (cells incubated at 43 degrees C for 30 min), and GM plus HS group, respectively. Lactate dehydrogenase (LDH) release increased time-dependently from 24 hr to 96 hr compared to the data of cells treated with GM only. Results of NAG activities, superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were similar to that of the LDH release. The amount of HSP72 positive cells increased significantly at 72 hr after cells were treated with GM only. Both HSP72 protein and gene expression increased significantly at 72 hr when cells were treated with GM. On the other hand, HS induced HSP72 expression markedly. Pretreatment of HS inhibited HK-2 cells from GM-induced injury. It could reduce LDH release and NAG activity. HS also increased SOD activity, and decreased MDA content when cells were damaged by GM. These findings suggested that HS may protect kidney cells from GM-induced injury. Pre-induction of HSP72 may provide therapeutic strategies for nephrotoxicity induced by GM.
Wang
Zhipeng
Z
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Liu
Li
L
Mei
Qibing
Q
Liu
Linna
L
Ran
Yuhua
Y
Zhang
Rong
R
D002478:Cells, Cultured; D019610:Cytoprotection; D005839:Gentamicins / Q000633:toxicity*; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism
D005839:Gentamicins; D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase