tailieunhanh - Báo cáo khoa học: The silencing of adenine nucleotide translocase isoform 1 induces oxidative stress and programmed cell death in ADF human glioblastoma cells

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 sig-nificant changes in ADF cell viability. | ỊFEBS Journal The silencing of adenine nucleotide translocase isoform 1 induces oxidative stress and programmed cell death in ADF human glioblastoma cells Annalisa Lena1 Mariarosa Rechichi1 Alessandra Salvetti1 Donatella Vecchio1 Monica Evangelista2 Giuseppe Rainaldi2 Vittorio Gremigni1 and Leonardo Rossi1 3 1 Dipartimento di Morfologia Umana e Biologia Applicata University of Pisa Italy 2 Laboratorio di Terapia Genica e Molecolare Istituto di Fisiologia Clinica CNR Pisa Italy 3 Istituto Toscano Tumori Italy Keywords adenine nucleotide translocase ADF cells glioblastoma multiforme mitochondrion reactive oxygen species Correspondence L. Rossi Dipartimento di Morfologia Umana e Biologia Applicata Sezione di Biologia e Genetica Via Volta 4 56126 Pisa Italy Fax 39 050 2219 101 Tel 39 050 2219 112 E-mail leoros@ These authors contributed equally to this work. Received 17 December 2009 revised 12 April 2010 accepted 28 April 2010 doi 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 .