Endogenous Hydrogen Peroxide Positively Regulates Secretion of a Gut-derived Peptide in Neuroendocrine Potentiation of the Oxidative Stress Response in

Overview

Journal bioRxiv

Date 2024 Sep 30

PMID 39345448

Authors

Qi Jia

Drew Young

Qixin Zhang

Derek Sieburth

Affiliations

Soon will be listed here.

Abstract

The gut-brain axis mediates bidirectional signaling between the intestine and the nervous system and is critical for organism-wide homeostasis. Here we report the identification of a peptidergic endocrine circuit in which bidirectional signaling between neurons and the intestine potentiates the activation of the antioxidant response in in the intestine. We identify a FMRF-amide-like peptide, FLP-2, whose release from the intestine is necessary and sufficient to activate the intestinal oxidative stress response by promoting the release of the antioxidant FLP-1 neuropeptide from neurons. FLP-2 secretion from the intestine is positively regulated by endogenous hydrogen peroxide (HO) produced in the mitochondrial matrix by /superoxide dismutase, and is negatively regulated by /peroxiredoxin, which depletes HO in both the mitochondria and cytosol. HO promotes FLP-2 secretion through the DAG and calciumdependent protein kinase C family member and by the SNAP25 family member in the intestine. Together, our data demonstrate a role for intestinal HO in promoting inter-tissue antioxidant signaling through regulated neuropeptide-like protein exocytosis in a gut-brain axis to activate the oxidative stress response.

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