Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy
Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy
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DOI：
10.1111/j.1471-4159.2010.06781.x
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发表时间：
2010-07-01
影响因子：
4.7
通讯作者：
Levin, Leonard A.
中科院分区：
文献类型：
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作者：
Kanamori, Akiyasu;Catrinescu, Maria-Magdalena;Levin, Leonard A.
p> corrole是一种四吡啶大环，由于其独特的氧化催化、还原催化和生物医学应用能力而受到越来越多的关注。腐蚀金属配合物（金属或角色）可以分解某些活性氧（ROS），类似于金属卟啉。我们研究了Fe-， Mn-和ga -corrole是否对神经元具有神经保护作用，并将其与体外和体内超氧化物清除活性联系起来。血清剥夺诱导视网膜神经节细胞-5神经元前体细胞凋亡。用3'-[1-[（苯胺）羰基]-3,4-四唑]-双（4-甲氧基-6-硝基）苯磺酸水合钠和钙黄蛋白- am /碘化丙啶测定细胞死亡。Fe-和mn -corrole，而非非氧化还原活性的Ga-corrole作为对照，减少了血清剥夺后RGC-5细胞的死亡。血清剥夺导致细胞内超氧化物水平升高，通过2-羟乙基铵荧光强度的增加检测到，这被Fe-和mn -corrole阻断，但不被Ga-corrole阻断。视神经横断后视网膜的体内实时共聚焦成像评估了单个大鼠视网膜神经节细胞内超氧化物的产生。Fe-和mn -corrole，而不是Ga-corrole，在体内清除神经元超氧化物。考虑到金属角色的神经保护活性与超氧化物清除活性相关，铁-和锰-角色可能是延迟视神经病变（如青光眼）轴突损伤后神经元死亡的候选药物。
P>Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose certain reactive oxygen species (ROS), similar to metalloporphyrins. We investigated whether Fe-, Mn-, and Ga-corroles have neuroprotective effects on neurons and correlated this with superoxide scavenging activity in vitro and in vivo. Apoptosis was induced in retinal ganglion cell-5 neuronal precursor cells by serum deprivation. Cell death was measured with sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate and calcein-AM/propidium iodide assays. Fe- and Mn-corroles, but not the non-redox-active Ga-corrole used as control, reduced RGC-5 cell death after serum deprivation. Serum deprivation caused increased levels of intracellular superoxide, detected by an increase in the fluorescence intensity of 2-hydroxyethidium, and this was blocked by Fe- and Mn-corroles, but not Ga-corrole. In vivo real-time confocal imaging of retinas after optic nerve transection assessed the superoxide production within individual rat retinal ganglion cells. Fe- and Mn-corroles, but not Ga-corrole, scavenged neuronal superoxide in vivo. Given that the neuroprotective activity of metallocorroles correlated with superoxide scavenging activity, Fe- and Mn-corroles could be candidate drugs for delaying neuronal death after axonal injury in optic neuropathies, such as glaucoma.