Document Detail

Mitochondrial superoxide production contribute to vancomycin-induced renal tubular cell apoptosis.
MedLine Citation:
PMID:  22401854     Owner:  NLM     Status:  Publisher    
Vancomycin chloride (VCM), a glycopeptide antibiotic, is widely used for the therapy of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, nephrotoxicity is the major adverse effect in VCM therapy. In the present study, we investigated the cellular mechanisms underlying VCM-induced renal tubular cell injury in cultured LLC-PK1 cells. VCM induced a concentration- and time-dependent cell injury in LLC-PK1 cells. VCM caused increases in the numbers of annexin V-positive /PI-negative cells and TUNEL-positive cells, indicating the involvement of apoptotic cell death in VCM-induced renal cell injury. The VCM-induced apoptosis was accompanied with the activation of caspase-9 and caspase-3/7, and reversed by these caspase inhibitors. Moreover, VCM caused increase in intracellular reactive oxygen species (ROS) production and mitochondrial membrane depolarization, which were reversed by vitamin E. In addition, the mitochondrial complexe I activity was inhibited by VCM as well as the complex I inhibitor rotenone, while rotenone mimicked the VCM-induced LLC-PK1 cell injury. These findings suggest that VCM causes apoptotic cell death in LLC-PK1 cells by enhancing mitochondrial superoxide production leading to mitochondrial membrane depolarization followed by the caspase activities. Moreover, the mitochondrial complex I may plays an important role in superoxide production and renal tubular cell apoptosis induced by VCM.
Yohei Arimura; Takahisa Yano; Megumi Hirano; Yuya Sakamoto; Nobuaki Egashira; Ryozo Oishi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-5
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
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