Sulforaphane inhibits mitochondrial permeability transition and oxidative stress.
Sulforaphane inhibits mitochondrial permeability transition and oxidative stress.
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DOI：
10.1016/j.freeradbiomed.2011.09.017
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发表时间：
2011-12-15
影响因子：
7.4
通讯作者：
Fiskum, Gary
中科院分区：
文献类型：
--
作者：
Greco, Tiffany;Shafer, Jonathan;Fiskum, Gary
关键词：
线粒体暴露于氧化应激和升高的Ca 2+促进线粒体通透性转换孔（PTP）的开放，导致膜去极化、氧化磷酸化解偶联和潜在的细胞死亡。本研究验证了以下假设：用萝卜硫素（SFP）（抗氧化剂基因表达的Nrf 2途径的激活剂）治疗大鼠，可增加肝线粒体对氧化还原调节的PTP开放的抵抗力，并提高线粒体抗氧化剂水平。给大鼠注射SFP或药物载体，40小时后分离肝线粒体。呼吸线粒体积极积累增加的Ca 2+，然后通过PTP开放释放的代理人，引起线粒体氧化还原状态的氧化转变或直接氧化蛋白质巯基。大鼠SFP治疗可抑制促氧化剂诱导的线粒体Ca 2+释放速率，并增加谷胱甘肽过氧化物酶/还原酶系统、硫氧还蛋白和苹果酸酶的表达。这些结果首次证明SFP治疗动物增加了肝脏线粒体抗氧化防御，并抑制了氧化还原敏感的PTP开放。这种新形式的预处理可以防止各种病理，包括氧化应激和线粒体功能障碍的病因。
Exposure of mitochondria to oxidative stress and elevated Ca2+ promotes opening of the mitochondrial permeability transition pore (PTP), resulting in membrane depolarization, uncoupling of oxidative phosphorylation, and potentially cell death. This study tested the hypothesis that treatment of rats with sulforaphane (SFP), an activator of the Nrf2 pathway of antioxidant gene expression, increases the resistance of liver mitochondria to redox-regulated PTP opening and elevates mitochondrial levels of antioxidants. Rats were injected with SFP or drug vehicle and liver mitochondria were isolated 40 hr later. Respiring mitochondria actively accumulated added Ca2+, which was then released through PTP opening induced by agents that either cause an oxidized shift in the mitochondrial redox state or that directly oxidize protein thiol groups. SFP treatment of rats inhibited the rate of pro-oxidant-induced mitochondrial Ca2+ release and increased expression of the glutathione peroxidase/reductase system, thioredoxin, and malic enzyme. These results are the first to demonstrate that SFP treatment of animals increases liver mitochondrial antioxidant defenses and inhibits redox-sensitive PTP opening. This novel form of preconditioning could protect against a variety of pathologies that include oxidative stress and mitochondrial dysfunction in their etiologies.
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影响因子：
7.4
作者：
Kowaltowski, AJ;Fenton, RG;Fiskum, G
通讯作者：
Fiskum, G
影响因子：
3.9
作者：
Halestrap, Andrew P.
通讯作者：
Halestrap, Andrew P.
影响因子：
64.8
作者：
Nakagawa, T;Shimizu, S;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.1
作者：
Balogun, E;Hoque, M;Motterlini, R
通讯作者：
Motterlini, R