Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition.
Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition.
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DOI：
10.1007/s10863-010-9312-9
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发表时间：
2010-12
影响因子：
3
通讯作者：
Fiskum, Gary
中科院分区：
文献类型：
--
作者：
Greco, Tiffany;Fiskum, Gary
氧化应激促进线粒体内膜通透性转换孔(PTP)依赖于钙离子的开放，在许多范例中导致生物能衰竭和随后的细胞死亡，包括与急性脑损伤相关的范例。一种对氧化应激进行预适应的方法是通过萝卜硫素(SFP)等药物激活抗氧化基因表达的Nrf2/ARE途径。这项研究测试了一种假设，即给正常大鼠服用SFP增加了分离的脑线粒体对氧化还原敏感的PTP开放的抵抗力。成年雄性大鼠在分离非突触脑线粒体前40h给予SFP或DMSO载体，剂量为10 mg/kg。线粒体悬浮在含有呼吸底物的介质中，并暴露于低于PTP开放阈值的钙离子的添加中。随后加入叔丁基氢过氧化氢(TBOOH)可导致环孢素A抑制的钙离子释放到培养液中，这是由培养液中钙绿5N的荧光增加监测的，在此之前线粒体NAD(P)H的自体荧光减弱，SFP处理显著降低了tBOOH诱导的钙释放速率，但不影响NAD(P)H的氧化，也不抑制直接羟基氧化剂苯基氧化砷诱导的PTP开放。SFP处理对脑线粒体的呼吸没有影响，直接加入分离的线粒体对PTP的开放和呼吸也没有影响。我们得出结论，SFP使脑线粒体对氧化还原调节的PTP开放具有抵抗，这可能有助于SFP观察到的神经保护作用。
Oxidative stress promotes Ca2+-dependent opening of the mitochondrial inner membrane permeability transition pore (PTP), causing bioenergetic failure and subsequent cell death in many paradigms, including those related to acute brain injury. One approach to preconditioning against oxidative stress is pharmacologic activation of the Nrf2/ARE pathway of antioxidant gene expression by agents such as sulforaphane (SFP). This study tested the hypothesis that administration of SFP to normal rats increases resistance of isolated brain mitochondria to redox-sensitive PTP opening. SFP or DMSO vehicle was administered intraperitoneally to adult male rats at 10 mg/kg 40 h prior to isolation of non-synaptic brain mitochondria. Mitochondria were suspended in medium containing a respiratory substrate and were exposed to an addition of Ca2+ below the threshold for PTP opening. Subsequent addition of tert-butyl hydroperoxide (tBOOH) resulted in a cyclosporin A-inhibitable release of accumulated Ca2+ into the medium, as monitored by an increase in fluorescence of Calcium Green 5N within the medium, and was preceded by a decrease in the autofluorescence of mitochondrial NAD(P)H. SFP treatment significantly reduced the rate of tBOOH-induced Ca2+ release but did not affect NAD(P)H oxidation or inhibit PTP opening induced by the addition of phenylarsine oxide, a direct sulfhydryl oxidizing agent. SFP treatment had no effect on respiration by brain mitochondria and had no effect on PTP opening or respiration when added directly to isolated mitochondria. We conclude that SFP confers resistance of brain mitochondria to redox-regulated PTP opening, which could contribute to neuroprotection observed with SFP.
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影响因子：
6.2
作者：
Danilov, Camelia A.;Chandirasekaran, Krish;Racz, Jennifer;Soane, Lucian;Zielke, Carol;Fiskum, Gary
通讯作者：
Fiskum, Gary
DOI：
10.1097/00004647-199904000-00010
发表时间：
1999-04-01
影响因子：
6.3
作者：
Okonkwo, DO;Povlishock, JT
通讯作者：
Povlishock, JT
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.7
作者：
Niizuma K;Endo H;Chan PH
通讯作者：
Chan PH
影响因子：
6.1
作者：
Angeloni, Cristina;Leoncini, Emanuela;Hrelia, Silvana
通讯作者：
Hrelia, Silvana