Matches in SemOpenAlex for { <https://semopenalex.org/work/W3048963208> ?p ?o ?g. }
- W3048963208 abstract "T cell activation depends from mitochondrial derived reactive oxygen species (mtROS). However, a thorough mechanistic knowledge of how and where mtROS acts in the signaling network of activated T cells is missing. This thesis aimed (i) to evaluate the mtROS signaling network in activated primary human T cells and (ii) to reveal the impact of mtROS signaling on immune phenotypes and effector functions. First, an mtROS inducible model based on primary human CD4+ T cells was established and probed with proteomics. By utilizing an isobaric thiol switching strategy, I performed a redox proteomic study quantifying cysteine residues susceptible to oxidation. 4784 cysteine-containing peptides could be assigned and quantified in this thesis. Of those, I identified 76 cysteine residues that were differentially oxidized upon T cell activation. Components of mitochondrial metabolism, cytoskeleton dynamics and zinc binding were enriched. As zinc finger proteins are known to mediate transcription/translation and can be modulated via the exclusion of the coordinated zinc ion which is known to dissociate following an increase in oxidative milieu I hypothesized an impact on protein turnover. To investigate mtROS-dependent translation, I employed the non-canonical amino acid (NCAAs), Azidohomoalanine (AHA), which incorporates into newly synthesized proteins and can be used to enrich translated proteins to explore changes in mtROS dependent protein transcription. 376 newly synthesized proteins from all conditions were identified, which allowed me to characterize the impact of mtROS on downstream transcription following activation. I identified two groups of proteins, which were antioxidants and proteins that upregulated NF-κB which is known to upregulate antioxidant processes and T cell activators which are known to be upregulated during T cell activation to modulate transcription factors, such as NFAT binding proteins. This work has highlighted the impact of mtROS on T cell expansion through NFAT and effector function through NF-κB. Taken together, this thesis has characterized the mechanistic impact of mtROS in T cell activation as well as the downstream regulatory processes, which constitute an mtROS dependent signaling network to achieve full T cell activation." @default.
- W3048963208 created "2020-08-18" @default.
- W3048963208 creator A5050930433 @default.
- W3048963208 date "2020-08-12" @default.
- W3048963208 modified "2023-09-26" @default.
- W3048963208 title "Respirasome-mediated Activation of T-Lymphocytes" @default.
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