MOTS-c attenuates hyperoxia-induced neonatal cardiac injury by inhibiting oxeiptosis via KEAP1-PGAM5 interaction

Neonatal cardiac injury is a significant concern in premature infants exposed to supplemental oxygen (hyperoxia), leading to long-term cardiovascular complications. Current therapies often focus on supportive care, but specific interventions to prevent or mitigate direct cardiac damage are limited. Oxeiptosis, a newly identified form of regulated cell death, is triggered by oxidative stress and involves the KEAP1-PGAM5 pathway, representing a critical, yet underexplored, mechanism in hyperoxia-induced damage. Understanding how to modulate this pathway could offer novel protective strategies for vulnerable neonatal hearts.

This study investigated the protective effects of MOTS-c against hyperoxia-induced cardiac injury. While specific experimental details like animal models, doses, routes, or durations are not provided in the abstract, the research likely employed both in vitro cellular models and in vivo neonatal animal models exposed to hyperoxic conditions. The primary focus was on assessing cardiac damage and the involvement of the oxeiptosis pathway, particularly the interaction between KEAP1 and PGAM5. Assays likely included markers of cell death, oxidative stress, and protein-protein interaction analysis.

The research concluded that MOTS-c effectively attenuates hyperoxia-induced neonatal cardiac injury. This protective effect was attributed to the peptide's ability to inhibit oxeiptosis, a specific form of regulated cell death. While the abstract does not provide specific numerical data such as percentages of reduction in injury markers, p-values, or fold-changes in protein expression, the overall conclusion points to a significant mechanistic role for MOTS-c in preserving cardiac health under oxidative stress. The study identifies a direct molecular mechanism through which MOTS-c exerts its protective actions. The core finding indicates that MOTS-c achieves this by maintaining the crucial interaction between the KEAP1 and PGAM5 proteins, thereby preventing the activation of the oxeiptotic cascade.