DOI: 10.1101/510438Jan 3, 2019Paper

Redox signaling via lipid peroxidation regulates retinal progenitor cell differentiation

BioRxiv : the Preprint Server for Biology
Shahad AlbadriFilippo Del Bene

Abstract

Reactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important secondary messengers in tissue homeostasis. However their regulation and mechanism of action remain poorly studied in vivo during normal development. Here we reveal that the fine regulation of hydrogen peroxide (H2O2) levels at the degradation step by its scavenger Catalase is crucial to mediate the switch from proliferation to differentiation in retinal progenitor cells (RPCs). We further show that altering the levels of downstream products of the Redox signaling can also affect this switch. Indeed, we identify 9-hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of this effect in the zebrafish retina. In fact, RPCs exposed to higher amounts of 9-HSA failed to differentiate and remained proliferative. We found that 9-HSA exerts its biological function in vivo by inhibiting the activity of histone deacetylase 1. We finally show that the local and temporal manipulation of H2O2 levels by catalase overexpression in RPCs was sufficient to trigger their premature differentiation. Therefore the amount of H2O2 in RPCs is instructive of their ability to switch from proliferation to differentiat...Continue Reading

Related Concepts

Catalase
Cell Differentiation Process
Hydrogen Peroxide
Lipid Peroxidation
Stem Cells
Zebrafish
Reactive Oxygen Species
Messenger protein
Local
9-hydroxystearic acid

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