Full metadata record
DC FieldValueLanguage
dc.contributor.authorLiu, Si-Yenen_US
dc.contributor.authorLiu, I-Chungen_US
dc.contributor.authorLin, Tiao-Yinen_US
dc.date.accessioned2017-04-21T06:56:45Z-
dc.date.available2017-04-21T06:56:45Z-
dc.date.issued2016-06en_US
dc.identifier.issn0263-6484en_US
dc.identifier.urihttp://dx.doi.org/10.1002/cbf.3180en_US
dc.identifier.urihttp://hdl.handle.net/11536/132577-
dc.description.abstractThioredoxin (Trx) is a redox protein characterized by a Trx fold. A naturally occurring truncated human Trx, Trx 80, which lacks the C-terminal strand-helix of the Trx fold, stimulates proliferation of peripheral blood mononuclear cells (PBMCs). It has not been clear how Trx80 gains this function. This study investigates whether a peptide with substantial sequence difference from Trx80, but retaining an abridged Trx fold can elicit PBMC proliferation. We genetically truncated a carboxy-terminal beta-alpha motif of Escherichia coli Trx to produce a peptide, Trx83, which shares low sequence identity with human Trx80. Addition of reduced-form Trx83 to resting human PBMCs promoted cell proliferation, while oxidized-form Trx83 lacked the function. By contrast, oxidized-form Trx80 exhibited a high activity in promoting PBMC proliferation, indicating the importance of sequence context of an abridged thioredoxin in influencing PBMC proliferation. Trx83 increases cellular reactive oxygen species and proinflammatory cytokines TNF-alpha and IL-1 beta, suggesting that Trx83 modulates inflammatory pathways. This notion is supported by the observation that cystine or cysteine abolishes the Trx83 induced PBMC proliferation. The PBMC stimulatory activity of Trx83 may have potential for pharmacological developments. SIGNIFICANCE OF THE STUDY Elicitation of primary proliferative responses of PBMCs by a protein is generally difficult. We show that Escherichia coli Trx83 with a truncated Trx fold induces PBMC proliferation, but only in the disulfide-reduced form. In contrast, oxidized-form human Trx80 is a potent stimulator. These results demonstrate that the sequence context of an abridged Trx fold is influential in inducing PBMC proliferation. The stimulatory effect of Trx83 is associated with an increase of inflammatory response. The possibility of eliciting PBMC proliferation and switching this activity on/off by redox control provides a perspective for developing Trx83 as a PBMC stimulatory agent. Copyright (C) 2016 John Wiley & Sons, Ltd.en_US
dc.language.isoen_USen_US
dc.subjecttruncated E. coli thioredoxinen_US
dc.subjectcell proliferationen_US
dc.subjectperipheral blood mononuclear cellsen_US
dc.subjectreactive oxygen speciesen_US
dc.subjectproinflammatory cytokinesen_US
dc.titleTruncated Escherichia coli thioredoxin induces proliferation of human blood mononuclear cells and production of reactive oxygen species as well as proinflammatory cytokinesen_US
dc.identifier.doi10.1002/cbf.3180en_US
dc.identifier.journalCELL BIOCHEMISTRY AND FUNCTIONen_US
dc.citation.volume34en_US
dc.citation.issue4en_US
dc.citation.spage226en_US
dc.citation.epage232en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000383368500005en_US
Appears in Collections:Articles