title: Increased GADD153 gene expression during iron chelation-induced apoptosis in Jurkat T-lymphocytes.
abstract: Depriving cells of iron likely stresses them and can result in cell death. To examine the potential relationship between this form of stress and cell death, Jurkat T-lymphocytes were made iron-deficient by exposing them to the iron chelator, deferoxamine (DFO). Such treatment produced evidence of apoptosis, including cell shrinkage, membrane blebbing, chromatin condensation and fragmentation, and also formation of apoptotic bodies. Additionally, proteolytic cleavage of poly(ADP-ribose)polymerase was detected, suggesting involvement of caspases in initiating apoptosis. Indeed, a selective caspase-3 inhibitor prevented the effects of DFO. During the early induction period of apoptosis, GRP78 and HSP70 mRNA expression was not affected. In contrast, there was mainly increased mRNA expression of Growth Arrest and DNA Damage-inducible gene 153 (GADD153), which seemed to be at the level of transcription rather than mRNA stability. Furthermore, fortifying cells with antioxidants did not prevent the increased GADD153 mRNA expression, and no evidence of single-strand breaks in DNA was found, suggesting that neither reactive oxygen species nor DNA damage was involved in triggering GADD153 gene activation. DFO also caused GADD153 protein to be expressed. Because GADD153 is recognized as a pro-apoptotic gene, these findings generate the notion that GADD153 might help mediate apoptosis in iron-deficient cells.
authors.affiliation: Cellular and Molecular Nutrition Research Laboratory, Graduate Program in Nutrition, The University of North Carolina at Greensboro, NC 27402-6170, USA.
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Pan
authors.forename: Robin G
authors.initials: RG
authors.lastname: Hopkins
authors.forename: George
authors.initials: G
authors.lastname: Loo
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage; D003676:Deferoxamine; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D000090463:Iron Deficiencies; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000975:Antioxidants; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D007502:Iron Chelating Agents; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003676:Deferoxamine