Redox Regulation of PPARγ in Polarized Macrophages
Joint Authors
Brühne, B.
Wittig, Ilka
Trümper, Verena
Heidler, Juliana
Richter, Florian
von Knethen, Andreas
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-01
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
The peroxisome proliferator-activated receptor (PPARγ) is a central mediator of cellular lipid metabolism and immune cell responses during inflammation.
This is facilitated by its role as a transcription factor as well as a DNA-independent protein interaction partner.
We addressed how the cellular redox milieu in the cytosol and the nucleus of lipopolysaccharide (LPS)/interferon-γ- (IFNγ-) and interleukin-4- (IL4-) polarized macrophages (MΦ) initiates posttranslational modifications of PPARγ, that in turn alter its protein function.
Using the redox-sensitive GFP2 (roGFP2), we validated oxidizing and reducing conditions following classical and alternative activation of MΦ, while the redox status of PPARγ was determined via mass spectrometry.
Cysteine residues located in the zinc finger regions (amino acid fragments AA 90-115, AA 116-130, and AA 160-167) of PPARγ were highly oxidized, accompanied by phosphorylation of serine 82 in response to LPS/IFNγ, whereas IL4-stimulation provoked minor serine 82 phosphorylation and less cysteine oxidation, favoring a reductive milieu.
Mutating these cysteines to alanine to mimic a redox modification decreased PPARγ-dependent reporter gene transactivation supporting a functional shift of PPARγ associated with the MΦ phenotype.
These data suggest distinct mechanisms for regulating PPARγ function based on the redox state of MΦ.
American Psychological Association (APA)
Trümper, Verena& Wittig, Ilka& Heidler, Juliana& Richter, Florian& Brühne, B.& von Knethen, Andreas. 2020. Redox Regulation of PPARγ in Polarized Macrophages. PPAR Research،Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1206636
Modern Language Association (MLA)
Trümper, Verena…[et al.]. Redox Regulation of PPARγ in Polarized Macrophages. PPAR Research No. 2020 (2020), pp.1-16.
https://search.emarefa.net/detail/BIM-1206636
American Medical Association (AMA)
Trümper, Verena& Wittig, Ilka& Heidler, Juliana& Richter, Florian& Brühne, B.& von Knethen, Andreas. Redox Regulation of PPARγ in Polarized Macrophages. PPAR Research. 2020. Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1206636
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206636