Hydrogen sulfide-releasing peptide attenuates autophagy-driven cellular injury in an experimental ischemic stroke...

Ischemic stroke is often linked to increased oxidative stress, impaired autophagy, and resultant cellular injury. This study examines the correlation between autophagy-mediated cellular injury and the use of a hydrogen sulfide (H₂S)-releasing peptide, SV-E4, to mitigate cellular damage resulting from oxygen-glucose deprivation (OGD), an in vitro model simulating ischemic stroke. The research employs neuroblastoma (N2a) and microglial (BV2) cell lines as well as 3-day developed chicken embryos. Elevated levels of pro-autophagic proteins corroborate our study's findings that OGD markedly enhances oxidative stress and triggers autophagy. Administration of the SV-E4 peptide formulation to cells subjected to OGD significantly reduced the amounts of reactive oxygen species. In the present investigation, dihydroethidium, Amplex Red, 2',7'-dichlorofluorescin diacetate, and mito-SOX were all utilized to corroborate conclusion. Decreased levels of autophagy markers indicated that the SV-E4 formulation could prevent aberrant autophagy. Notably, this mechanism is not limited to ischemic stroke but extends to other ischemia-reperfusion models, as demonstrated using an in ovo ischemia-reperfusion model in chicken embryos. Altogether, the results indicate that the SV-E4 peptide has a beneficial impact on preventing excessive oxidative stress and autophagy, demonstrating its potential as a treatment approach for individuals with ischemic stroke.