Document Detail


Resistance of mtDNA-depleted cells to apoptosis.
MedLine Citation:
PMID:  18302187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells lacking mitochondrial genome (defined as rho(0)) are useful models in studies on cancer, aging, mitochondrial diseases and apoptosis, but several of their functional aspects have been poorly characterized. Using different clones of rho(0) cells derived from the human osteosarcoma line 143B, we have tested the effects of different apoptogenic molecules such as staurosporine (STS), doxorubicin, daunomycin and quercetin, and have analyzed apoptosis, mitochondrial membrane potential (MMP), levels of oxygen free radicals, reduced glutathione (GSH) content, and expression of P-glycoprotein (P-gp). When compared to parental cells, rho(0) cells resulted much less sensitive to apoptosis. MMP was well maintained in rho(0) cells, and remained unchanged after adding apoptogenic agents, and did not change after treatment with molecules able to depolarize mitochondria such as valinomycin. After adding STS, the production of reactive oxygen species was similar in both cell types, but rho(0) cells maintained higher levels of GSH. In rho(0) cells, P-gp was strongly over-expressed both at mRNA and protein level, and its functionality was higher. The resistance to apoptosis of rho(0) cells could be not only due to an increased scavenger capacity of GSH, but also due to a selection of multidrug resistant cells that hyperexpress P-gp.
Authors:
Roberta Ferraresi; Leonarda Troiano; Marcello Pinti; Erika Roat; Enrico Lugli; Daniela Quaglino; Daniela Taverna; Dina Bellizzi; Giuseppe Passarino; Andrea Cossarizza
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cytometry. Part A : the journal of the International Society for Analytical Cytology     Volume:  73     ISSN:  1552-4930     ISO Abbreviation:  Cytometry A     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-27     Completed Date:  2008-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235694     Medline TA:  Cytometry A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  528-37     Citation Subset:  IM    
Copyright Information:
(c) 2008 International Society for Advancement of Cytometry.
Affiliation:
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Cell Line, Tumor
DNA, Mitochondrial / metabolism*
Free Radicals / metabolism
Gene Expression
Glutathione / biosynthesis
Humans
Membrane Potential, Mitochondrial / physiology
Microscopy, Electron, Transmission
Mitochondria / metabolism*,  ultrastructure*
Multidrug Resistance-Associated Proteins / metabolism
P-Glycoprotein / biosynthesis,  metabolism
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Free Radicals; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/RNA, Messenger; 0/multidrug resistance-associated protein 1; 70-18-8/Glutathione

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