Kisspeptin-10 alleviates OGD/R-induced H9c2 cardiomyocyte injury by triggering autophagy via regulating the YY1/TFEB axis.
Kisspeptin-10 may enhance autophagy and alleviate injury in heart cells exposed to ischemia-reperfusion, but further validation in animal models is necessary.
Where it sits
this study against the rest of the kisspeptin (kp-10) corpusSummary and findings
Kisspeptin-10 (Kp-10) was investigated for its effects on OGD/R-induced injury in H9c2 cardiomyocytes. Cells were treated with 50 or 100 nM Kp-10 after OGD/R exposure. The study found that Kp-10 may alleviate cellular injury by enhancing autophagy.
Abstract
Myocardial ischemia-reperfusion injury (MIRI) is characterized by exacerbated myocardial damage following the restoration of blood flow after myocardial ischemia, owing to factors such as increased production of reactive oxygen species, calcium overload, and inflammatory responses. Induction of cellular autophagy has been reported to alleviate MIRI. Kisspeptin-10 (Kp-10) is a short peptide produced by hydrolysis of the precursor protein encoded by the KISS1 gene and has shown promising autophagy-inducing properties. Here, the effects of Kp-10 on OGD/R-induced injury were investigated in H9c2 cardiomyocytes using an in vitro model relevant to MIRI. H9c2 cardiomyocytes were treated with OGD/R, followed by incubation with 50 or 100 nM Kp-10. Markedly reduced cell viability, an increased apoptotic rate and MDA levels, and diminished SOD and CAT activities were observed in OGD/R-stimulated H9c2 cardiomyocytes. These changes were accompanied by downregulated LC3-II/I, ATG5, and Beclin1, decreased nuclear levels of YY1 and TFEB, and reduced transcriptional activities of YY1 and TFEB, all of which were remarkably reversed by Kp-10. Moreover, the effects of Kp-10 on cell viability, oxidative stress, and the expression of autophagy-related proteins were substantially abolished by silencing YY1 or TFEB. Collectively, Kp-10 attenuated OGD/R-induced H9c2 cardiomyocyte injury in vitro, possibly by enhancing autophagy through the YY1/TFEB axis. These findings provide a cellular basis for further investigation of Kp-10 in MIRI, although validation in animal models is required before its clinical relevance can be assessed.<h4>Supplementary information</h4>The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01089-2.
Background
This paper addresses the issue of myocardial ischemia-reperfusion injury (MIRI), a condition that leads to significant myocardial damage upon restoration of blood flow. Previous research has indicated that inducing autophagy may alleviate MIRI. Kisspeptin-10 (Kp-10) is noted for its autophagy-inducing properties, making it a candidate for further investigation in this context.
Methods
The study utilized an in vitro model involving H9c2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Cells were treated with Kp-10 at doses of 50 or 100 nM. Primary outcome measures included cell viability, apoptotic rate, and levels of oxidative stress markers.
Results
Kp-10 treatment resulted in markedly reduced cell viability in OGD/R-stimulated H9c2 cardiomyocytes. The study also reported increased apoptotic rates and elevated MDA levels, alongside diminished SOD and CAT activities. Additionally, Kp-10 reversed the downregulation of autophagy-related proteins such as LC3-II/I, ATG5, and Beclin1.
Interpretation
While the findings indicate that Kp-10 may enhance autophagy and alleviate cellular injury, the effect sizes and clinical significance remain unclear. The study's in vitro nature and reliance on a single cell line limit the generalizability of the results. Further research is needed to validate these findings in animal models and assess potential clinical applications.
Key findings
- 50 or 100 nM Kp-10 treatment markedly reduced cell viability in OGD/R-stimulated H9c2 cardiomyocytes.
- Increased apoptotic rate and MDA levels were observed in OGD/R-stimulated H9c2 cardiomyocytes.
- SOD and CAT activities were diminished in OGD/R-stimulated H9c2 cardiomyocytes.
- Kp-10 reversed downregulated LC3-II/I, ATG5, and Beclin1 in OGD/R-stimulated H9c2 cardiomyocytes.
- Kp-10 effects on cell viability and oxidative stress were abolished by silencing YY1 or TFEB.
Limitations
- In vitro study using H9c2 cardiomyocytes.
- No clinical data or human trials reported.
- Effects observed may not translate to in vivo conditions.
- Further validation in animal models required.