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dc.contributor.authorAlikhani, Manien_US
dc.contributor.authorRoy, Sayonen_US
dc.contributor.authorGraves, Dana T.en_US
dc.date.accessioned2012-01-09T20:58:40Z
dc.date.available2012-01-09T20:58:40Z
dc.date.copyright2010en_US
dc.date.issued2010-3-10en_US
dc.identifier.citationAlikhani, Mani, Sayon Roy, Dana T. Graves. "FOXO1 plays an essential role in apoptosis of retinal pericytes" Molecular VIsion 16:408-415. (2010)en_US
dc.identifier.issn1090-0535en_US
dc.identifier.urihttps://hdl.handle.net/2144/2952
dc.description.abstractPURPOSE. An early and significant event in diabetic retinopathy is the loss of retinal microvascular pericytes. Studies were performed to investigate pathways through which an advanced glycation endproduct and tumor necrosis factor (TNF)-α stimulate apoptosis in retinal pericytes through the activation of the pro-apoptotic transcription factor Forkhead box O1 (FOXO1). METHODS. Human retinal pericytes were stimulated by carboxymethyllysine (CML)-collagen, an advanced glycation endproduct, or TNF-α in vitro. Apoptosis was assessed by measuring cytoplasmic histone-associated DNA. The role of FOXO1 was examined by RNA interference (RNAi), and specific inhibitors were used to investigate the role of p38 and Jun N-terminal kinase mitogen-activated protein kinase (JNK MAP) kinases, Akt, and nuclear factor kappa B (NF-κB). Caspase-3 activity was measured with a luminescent substrate, and FOXO1 DNA-binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS. TNF-α and CML-collagen but not control collagen stimulated apoptosis, caspase-3 activity, and FOXO1 DNA-binding activity in pericytes. Silencing FOXO1 by small interfering RNA prevented apoptosis of pericytes in response to both TNF-α and CML-collagen. By use of specific inhibitors, we demonstrated that both FOXO1 activation and subsequent apoptosis was mediated, in part, by p38 and JNK MAP kinases. In contrast Akt and NF-κB inhibitors had the opposite effect on pericyte apoptosis. CONCLUSIONS. The results demonstrate pathways through which two different mediators, TNF-α and an advanced glycation endproduct, can induce pericyte apoptosis through activation of the transcription factor FOXO1.en_US
dc.description.sponsorshipNational Institutes of Health (R01DE017732, R01DE019108, R01EY014702)en_US
dc.language.isoenen_US
dc.publisherMolecular Visionen_US
dc.rightsCopyright 2010 Molecular Vision.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.titleFOXO1 Plays an Essential Role in Apoptosis of Retinal Pericytesen_US
dc.typeArticleen_US
dc.identifier.pmid20300563en_US
dc.identifier.pmcid2838737en_US


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Copyright 2010 Molecular Vision.
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