Mitochondrial-targeted SS-31 peptide attenuates radiation-induced cardiomyocyte senescence.
SS-31 treatment reduced markers of cell senescence in cardiomyoblasts exposed to radiation, but the clinical significance of these findings in humans is unclear.
Where it sits
this study against the rest of the ss-31 corpusSummary and findings
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell-derived cardiomyocytes. SS-31 was administered at a dose of 1 μM for 7 days. The treatment resulted in a reduction of senescence-associated beta-galactosidase positive staining from 67% to 38% in H9C2 cells exposed to 10 Gy of radiation.
Abstract
Exposure to ionizing radiation, such as from radiation therapy or accidental radiation exposure can have adverse effects on the heart. While radiation injury in the heart may include cardiomyocyte senescence, there are no available strategies to prevent this phenomenon. This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Exposure to γ-radiation at doses of 2, 5, and 10 Gy inhibited H9C2 cell proliferation in a dose-dependent manner, and induced senescence-associated beta-galactosidase (SA-β-gal) staining, a gold standard of cell senescence. Treatment with SS-31 (1 μM) for 7 days reduced SA-β-gal positive staining from 67% to 38% in H9C2 cells under 10 Gy radiation. SS-31 also prevented increases in the expression of p16 and p21, two well-accepted senescence markers, in irradiated H9C2 cells and hiPSC-CMs. SS-31 decreased the canonical senescence-associated secretory phenotype markers TNF-α, IL-6, and IL-1β. SS-31 also reversed the BAX/bcl-2 ratio, a marker of mitochondrial-related apoptosis. Moreover, SS-31 mitigated mitochondrial production of reactive oxygen species. Interestingly, we found that a dose of 10 Gy increased mitochondrial respiration, and SS-31 reversed this elevation. This study suggests that SS-31 is a promising compound that may prevent radiation-induced cardiomyocyte senescence.
Background
The paper addresses the impact of radiation on cardiomyocytes, specifically focusing on the senescence process induced by radiation exposure. Prior research has indicated that radiation can lead to cellular damage and senescence, contributing to cardiovascular diseases. This study is significant as it explores a potential intervention using the SS-31 peptide to mitigate these effects.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.