Publication:
Dependence of reactive oxygen species and FLICE inhibitory protein on Lipofectamine-induced apoptosis in human lung epithelial cells

dc.contributor.authorLalana Kongkaneramiten_US
dc.contributor.authorNarong Sarisutaen_US
dc.contributor.authorNeelam Azaden_US
dc.contributor.authorYongju Luen_US
dc.contributor.authorAnand Krishnan V. Iyeren_US
dc.contributor.authorLiying Wangen_US
dc.contributor.authorYon Rojanasakulen_US
dc.contributor.otherWest Virginia Universityen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherNational Institute for Occupational Safety and Healthen_US
dc.contributor.otherWest Virginia University Robert C. Byrd Health Sciences Centeren_US
dc.date.accessioned2018-07-12T02:18:28Z
dc.date.available2018-07-12T02:18:28Z
dc.date.issued2008-06-01en_US
dc.description.abstractCationic liposomes such as Lipofectamine (LF) are widely used as nonviral gene delivery vectors; however, their clinical application is limited by their cytotoxicity. These agents have been shown to induce apoptosis as the primary mode of cell death, but their mechanism of action is not well understood. The present study investigated the mechanism of LF-induced apoptosis and examined the role of reactive oxygen species (ROS) in this process. We found that LF induced apoptosis of human epithelial H460 cells through a mechanism that involves caspase activation and ROS generation. Inhibition of caspase activity by pan-caspase inhibitor (z-VAD-fmk) or by specific caspase-8 inhibitor (z-IETD-fmk) or caspase-9 inhibitor (z-LEHD-fmk) inhibited the apoptotic effect of LF. Overexpression of FLICE-inhibitory protein (FLIP) or B-cell lymphoma-2, which are known inhibitors of the extrinsic and intrinsic death pathways, respectively, similarly inhibited apoptosis by LF. Induction of apoptosis by LF was shown to require ROS generation because its inhibition by ROS scavengers or by ectopic expression of antioxidant enzyme superoxide dismutase and glutathione peroxidase strongly inhibited the apoptotic effect of LF. Electron spin resonance studies showed that LF induced multiple ROS; however, superoxide was found to be the primary ROS responsible for LF-induced apoptosis. The mechanism by which ROS mediate the apoptotic effect of LF involves down-regulation of FLIP through the ubiquitination pathway. In demonstrating the role of FLIP and ROS in LF death signaling, we document a novel mechanism of apoptosis regulation that may be exploited to decrease cytotoxicity and increase gene transfection efficiency of cationic liposomes.en_US
dc.identifier.citationJournal of Pharmacology and Experimental Therapeutics. Vol.325, No.3 (2008), 969-977en_US
dc.identifier.doi10.1124/jpet.107.136077en_US
dc.identifier.issn15210103en_US
dc.identifier.issn00223565en_US
dc.identifier.other2-s2.0-44249116184en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/20.500.14594/18913
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=44249116184&origin=inwarden_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleDependence of reactive oxygen species and FLICE inhibitory protein on Lipofectamine-induced apoptosis in human lung epithelial cellsen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=44249116184&origin=inwarden_US

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