β-ECDYSTERONE MODULATES MAMMALIAN CELL BIOENERGETICS AND ATTENUATES MPTP-ASSOCIATED MITOCHONDRIAL DEPOLARIZATION
Abstract
Ecdysterone, or 20-hydroxyecdysone, is a naturally occurring ecdysteroid widely distributed in plants and known to exert biological effects in mammals. We have previously shown that ecdysterone stimulates mitochondrial bioenergetics in intact cells, but has no substantial effect on isolated mitochondria, suggesting that its action may depend on cellular regulatory mechanisms. Here, we examined whether ecdysterone modulates activation of the mitochondrial permeability transition pore (mPTP) in intact cells. Human SH-SY5Y neuroblastoma cells were used as an experimental model. Ferutinin, a natural estrogen, was applied at 25 µM to induce mPTP-associated mitochondrial depolarization. Mitochondrial membrane potential was assessed by fluorescence microscopy using TMRM. Ferutinin induced pronounced mitochondrial depolarization, which was markedly suppressed by cyclosporin A, a selective mPTP inhibitor, confirming the involvement of the permeability transition pore. These findings suggest that ecdysterone lowers mitochondrial sensitivity to Ca2⁺-dependent stress in intact cells. However, its protective efficacy was lower than that of cyclosporin A, indicating that ecdysterone is unlikely to act as a direct mPTP inhibitor. Instead, its effect may be mediated indirectly through cellular mechanisms that regulate mitochondrial bioenergetics and resistance to permeability transition.
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