Document Detail


The silencing of adenine nucleotide translocase isoform 1 induces oxidative stress and programmed cell death in ADF human glioblastoma cells.
MedLine Citation:
PMID:  20528917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenine nucleotide translocases (ANTs) are multitask proteins involved in several aspects of cell metabolism, as well as in the regulation of cell death/survival processes. We investigated the role played by ANT isoforms 1 and 2 in the growth of a human glioblastoma cell line (ADF cells). The silencing of ANT2 isoform, by small interfering RNA, did not produce significant changes in ADF cell viability. By contrast, the silencing of ANT1 isoform strongly reduced ADF cell viability by inducing a non-apoptotic cell death process resembling paraptosis. We demonstrated that cell death induced by ANT1 depletion cannot be ascribed to the loss of the ATP/ADP exchange function of this protein. By contrast, our findings indicate that ANT1-silenced cells experience oxidative stress, thus allowing us to hypothesize that the effect of ANT1-silencing on ADF is mediated by the loss of the ANT1 uncoupling function. Several studies ascribe a pro-apoptotic role to ANT1 as a result of the observation that ANT1 overexpression sensitizes cells to mitochondrial depolarization or to apoptotic stimuli. In the present study, we demonstrate that, despite its pro-apoptotic function at a high expression level, the reduction of ANT1 density below a physiological baseline impairs fundamental functions of this protein in ADF cells, leading them to undertake a cell death process.
Authors:
Annalisa Lena; Mariarosa Rechichi; Alessandra Salvetti; Donatella Vecchio; Monica Evangelista; Giuseppe Rainaldi; Vittorio Gremigni; Leonardo Rossi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-27
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2853-67     Citation Subset:  IM    
Affiliation:
Dipartimento di Morfologia Umana e Biologia Applicata, University of Pisa, Pisa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adenine Nucleotide Translocator 1 / genetics*,  metabolism
Apoptosis*
Gene Silencing*
Glioblastoma / enzymology,  metabolism*,  pathology*
Humans
Oxidative Stress*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Adenine Nucleotide Translocator 1

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


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