Document Detail


The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells.
MedLine Citation:
PMID:  21553225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study is to explore the mechanism by which acrolein (ACR), a metabolite of cyclophosphamide (CP), induces immature Sertoli cell cytoskeletal changes. Sertoli cells obtained from rats were cultivated and treated with 50 and 100 μM ACR. XTT assays were performed to detect cell viability. Activities of superoxide dismutase (SOD), glutathione peroxidases (GSH-Px), and catalase (CAT), as well as total anti-oxidation competence (T-AOC) were examined. Superoxide anion levels were detected by a fluorescent probe. Cell ultrastructure changes were observed by transmission fluorescent microscope. Actin filament (F-actin) distribution was detected by immunofluorescence, and ERK and p38MAPK expression were detected by western blot analysis. ACR significantly decreased the viability of Sertoli cells in a dose- and time-dependent manner. T-AOC and the antioxidant activity of SOD, CAT and GSH-Px, were decreased in ACR-treated groups compared with the control group. The levels of reactive oxygen species (ROS) in ACR-treated Sertoli cells were increased. In addition, characteristics of cell apoptosis such as mitochondrial swelling, aggregated chromatin, condensed cytoplasm, nuclei splitting, and nuclei vacuolization were observed in ACR-treated cells. Furthermore, ACR-treatment also induced microfilament aggregation, marginalization and regionalization. The expression levels of ERK and p38MAPK were also increased in ACR-treated cells in a dose- and time-dependent manner. ACR, a major CP metabolite, impairs the cytoskeleton which is likely caused by induction of the oxidative stress response through up-regulation of ERK and p38MAPK expression.
Authors:
Feng Liu; Xu-Liang Li; Tao Lin; Da-Wei He; Guang-Hui Wei; Jun-Hong Liu; Lu-Sheng Li
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Publication Detail:
Type:  Journal Article     Date:  2011-05-08
Journal Detail:
Title:  Molecular biology reports     Volume:  39     ISSN:  1573-4978     ISO Abbreviation:  Mol. Biol. Rep.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-11-22     Completed Date:  2012-03-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0403234     Medline TA:  Mol Biol Rep     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  493-500     Citation Subset:  IM    
Affiliation:
The Department of Pediatric Urology, Ministry of Education, Key Laboratory of Child Development and Disorders, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2 RD, Yuzhong District, Chongqing, 400014, China. cchliuf@163.com
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MeSH Terms
Descriptor/Qualifier:
Acrolein / metabolism,  pharmacology*
Analysis of Variance
Animals
Blotting, Western
Catalase / metabolism
Cyclophosphamide / metabolism
Cytoskeleton / drug effects*
Dose-Response Relationship, Drug
Fluorescent Antibody Technique
Glutathione Peroxidase / metabolism
Male
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Oxidative Stress / drug effects*
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Sertoli Cells / drug effects*,  physiology,  ultrastructure
Superoxide Dismutase / metabolism
Tetrazolium Salts
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Tetrazolium Salts; 107-02-8/Acrolein; 117038-70-7/2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; 50-18-0/Cyclophosphamide; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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