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Identifier

000441321

Title

Dissecting the role of macrophages in glucose systemic metabolism upon DNA damage

Alternative Title

Μελέτη του ρόλου των μακροφάγων στο συστημικό μεταβολισμό της γλυκόζης μετά από συσσώρευση γενετικών βλαβών

Author

Σταυγιαννουδάκη, Ιωάννα Ε.

Thesis advisor

Γαρίνης, Γεώργιος

Abstract

Accumulation of DNA damages can lead to changes at both molecular and cellular level. These changes can have an impact not only on the cells that bear the DNA lesions, but also on other cells with which they communicate. One example is infiltrating macrophages which upon knock out of a basic DNA repair protein, ERCC1, have the capability to cause changes in the glucose systemic metabolism through exosome secretion (Goulielmaki et al., 2020). In more detail, accumulation of DNA damages which occurs due to dysfunctional DNA repairing system results in the production of exosomes, which are received by target cells and trigger increased glucose absorbance through a specific type of transporter, GLUT1. It is worth mentioning that this cellular response is independent of insulin signaling. The elevated intracellular glucose levels contribute to activation of TOR pathway, among the other cellular modifications they stimulate. This project’s purpose was to clarify the type of the macromolecule that is responsible for the metabolic reprogramming of the recipient cells as well as to emphasize all the cellular aspects that are affected by exosomes. We drew the conclusion that the leading molecules in the metabolic changes in the recipient cells are the exosomal proteins. The proteome of the exosomes is consisted of 5266 proteins in total, which, with the aid of computational analysis, we managed to categorize to particular pathways. The most over-representative pathways that stood out are pathways related to immune response, transcription, cytoskeletal rearrangements and splicing. The computational estimations were verified by experimental set-ups through which we impeded each process and we observed how glucose influx was altered.

Language

English

Subject

Cytoskeleton

GLUT-1

Transcription

c-MVC

Κυτταροσκελετός

Μεταγραφή

Issue date

2021-07-30

Collection