Hydrogen sulfide protects against spinal cord pyroptosis via persulfidation of Rac1 after lumbosacral plexus nerve injury.

ABSTRACT: Pyroptosis, a form of lytic and inflammatory programmed cell death mediated by gasdermin proteins, contributes to progressive spinal cord neurodegeneration following neural trauma. Nevertheless, the regulatory mechanisms governing this process remain inadequately characterized. In this investigation, hydrogen sulfide (H₂S) was identified as an endogenous inhibitor of neuronal pyroptosis, functioning through Rac1-dependent NLRP3 inflammasome signaling. In a rat model of lumbosacral plexus nerve injury, H₂S treatment significantly decreased pyroptosis-associated markers (NLRP3, caspase-1, GSDMD) and enhanced neuronal survival. In vitro, the administration of H₂S effectively mitigated hypoxia-induced neuronal pyroptosis by inhibiting the assembly of the NLRP3 inflammasome. Mechanistically, ou

SUBMITTER: Mao J 

PROVIDER: S-EPMC12500895 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature