Hydrogen Peroxide Regulates Protein N-Glycosylation

Authors

• Alexandria Hernandez-Nichols, University of Alabama at Birmingham

Advisor(s)

Rakesh Patel

Committee Member(s)

Hubert Tse
Jarrod Barnes
Karina Yoon
Rajasekaran Soorapan
Timmy Lee

School

Joint Health Sciences (Interdisciplinary)

Document Type

Dissertation

Department (new version)

Pathology

Date of Award

9-9-2024

Abstract

N-glycosylation is a co- and post-translational modification wherein a variety of sugars are added to proteins in a linear pathway progressing from high mannose (HM) to hybrid, to complex type N-glycans. This modification is important to the understanding of protein maturation, stability, and function. Studies have shown that changes in cell N-glycomes, in particular, the HM N-glycan category, could be hallmarks of various pathologies. The biosynthetic pathway for N-glycosylation is well studied and the key enzymes involved in the progression of HM to hybrid N-glycans are the a-mannosidases. Little is understood about the regulation of this highly complex post-translational modification system, though. Herein, we hypothesize that redox signaling, specifically H2O2, regulates the formation of HM N-glycans. This study demonstrates, 1) the role for ER compartment H2O2 in endothelial cells in formation of HM N-glycans that are then expressed at the cell surface, 2) the mechanism by which ER H2O2 forms HM N-glycans via decreased a-mannosidase activity, and 3) a role for H2O2 in regulating HM N-glycans in non-compartmentalized cells. Taken together, the findings of this study add valuable insights into the regulation of N-glycosylation machinery, formation of HM N-glycans and functional changes that can arise from altering this subset of N-glycans.

ProQuest ID

https://proquest.com/docview/3101909035