| RRC ID |
84140
|
| Author |
Jia Q, Young D, Zhang Q, Sieburth D.
|
| Title |
Endogenous hydrogen peroxide positively regulates secretion of a gut-derived peptide in neuroendocrine potentiation of the oxidative stress response in Caenorhabditis elegans.
|
| Journal |
Elife
|
| 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 Caenorhabditis elegans in the intestine. We identify an 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 (H2O2) produced in the mitochondrial matrix by sod-3/superoxide dismutase, and is negatively regulated by prdx-2/peroxiredoxin, which depletes H2O2 in both the mitochondria and cytosol. H2O2 promotes FLP-2 secretion through the DAG and calcium-dependent protein kinase C family member pkc-2 and by the SNAP25 family member aex-4 in the intestine. Together, our data demonstrate a role for intestinal H2O2 in promoting inter-tissue antioxidant signaling through regulated neuropeptide-like protein exocytosis in a gut-brain axis to activate the oxidative stress response.
|
| Volume |
13
|
| Published |
2024-12-5
|
| DOI |
10.7554/eLife.97503
|
| PII |
97503
|
| PMID |
39636673
|
| PMC |
PMC11620748
|
| MeSH |
Animals
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans* / physiology
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Hydrogen Peroxide* / metabolism
Neurons / metabolism
Neuropeptides / metabolism
Oxidative Stress*
Signal Transduction
Superoxide Dismutase / metabolism
|
| Resource |
| C.elegans |
tm4085
tm2820
tm3351
tm783
tm1146
tm760 |
