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Exploiting the role of resveratrol in rat mitochondrial permeability transition
Yue Zhang1, Fangfang Tian, Qi Xiao
1State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
Abstract:
Resveratrol (RSV), a natural polyphenolic antioxidant, has been considered an anticarcinogenic agent as it triggers tumor cell apoptosis through activation of the mitochondrial pathway. In our study, the effects of RSV on mitochondria, especially on the mitochondrial permeability transition (MPT) process, were investigated by multiple methods. We found that RSV induced a collapse of membrane potential and matrix swelling related to MPT. We further demonstrated that Ca²⁺ was necessary for this RSV-induced MPT opening. In addition, RSV induced the inner membrane permeabilization to H⁺ and K⁺, the depression of respiration and changes in membrane fluidity. The results suggested that RSV-induced MPT was accompanied by mitochondrial dysfunction. But the prohibition on lipid peroxidation and different effects of low- and high-dose RSV on membrane fluidity and respiration showed that the interaction of RSV and the mitochondria could not be the result of a single simple mechanism.
Insights
Resveratrol (RSV) triggers mitochondrial permeability transition (MPT), causing cell death. This study shows RSV-induced MPT requires calcium ions and leads to mitochondrial dysfunction, but RSV
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial Research
Background:
- Resveratrol (RSV), a natural antioxidant, shows anticarcinogenic potential by inducing tumor cell apoptosis via mitochondrial pathways.
- Understanding RSV's precise effects on mitochondria is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the effects of Resveratrol (RSV) on mitochondrial function, focusing on the mitochondrial permeability transition (MPT) process.
- To elucidate the role of calcium ions (Ca²⁺) in RSV-induced MPT.
- To explore the complex interactions between RSV and mitochondrial membranes.
Main Methods:
- Assessment of mitochondrial membrane potential and matrix swelling.
- Investigation of Ca²⁺ dependency for MPT induction.
- Measurement of inner membrane proton (H⁺) and potassium (K⁺) permeability.
- Analysis of respiratory function and membrane fluidity.
- Evaluation of lipid peroxidation inhibition.
Main Results:
- RSV induced MPT, evidenced by membrane potential collapse and matrix swelling.
- Calcium ions (Ca²⁺) were essential for initiating RSV-induced MPT.
- RSV caused inner membrane permeabilization to H⁺ and K⁺, decreased respiration, and altered membrane fluidity.
- RSV inhibited lipid peroxidation, and its effects on fluidity and respiration varied with dose.
- These findings suggest a complex, multi-mechanistic interaction between RSV and mitochondria.
Conclusions:
- RSV-induced MPT contributes to mitochondrial dysfunction and potential cell death.
- The interaction of RSV with mitochondria is complex, involving Ca²⁺-dependent MPT and dose-dependent effects.
- RSV's multifaceted effects on mitochondria warrant further investigation for cancer therapy development.
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