Superoxide signaling and cell death in retinal ganglion cell axotomy: effects of metallocorroles.
Superoxide signaling and cell death in retinal ganglion cell axotomy: effects of metallocorroles.
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DOI：
10.1016/j.exer.2012.02.006
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发表时间：
2012-04
影响因子：
3.4
通讯作者：
Levin LA
中科院分区：
文献类型：
--
作者：
Catrinescu MM;Chan W;Mahammed A;Gross Z;Levin LA
视神经内视网膜神经节细胞(RGC)轴突的损伤会导致胞体的凋亡。我们以前曾证明，在体内，轴突切断会导致RGC胞体内超氧阴离子的升高，这种情况发生在Annexin-V阳性的1-2天之前，Annexin-V是细胞凋亡的标志。聚乙二醇化的超氧化物歧化酶输送到RGC可防止超氧化物歧化，挽救胞体。综上所述，这些结果表明，超氧化物是视网膜节细胞轴突损伤后细胞凋亡的上游信号。然后，我们研究了金属配位、有效的超氧化物歧化酶模拟物，我们已经证明它在体外具有神经保护作用，以及在体内对视网膜神经节细胞具有超氧化物清除剂。用荧光染料4Di-10Asp逆行标记视网膜节细胞，行眶内视神经切断。将Fe(III)2，17-bis-sulfonato-5，10，15-tris(pentafluorophenyl)corrole(Fe(Tpfc)(SOH)2)(Fe-Corole)注入玻璃体内。对视网膜节细胞进行纵向成像，并计数存活视网膜节细胞的数量。含有铁的标记的RGC存活率显著提高，但神经保护程度相对低于它们清除超氧化物的能力--这意味着活性氧对细胞凋亡的信号转导具有意想不到的复杂性。
Injury to retinal ganglion cell (RGC) axons within the optic nerve causes apoptosis of the soma. We previously demonstrated that in vivo axotomy causes elevation of superoxide anion within the RGC soma, and that this occurs 1–2 days before annexin-V positivity, a marker of apoptosis. Pegylated superoxide dismutase delivery to the RGC prevents the superoxide elevation and rescues the soma. Together, these results imply that superoxide is an upstream signal for apoptosis after axonal injury in RGCs. We then studied metallocorroles, potent superoxide dismutase mimetics, which we had shown to be neuro-protective in vitro and superoxide scavengers in vivo for RGCs. RGCs were retrograde labeled with the fluorescent dye 4Di-10Asp, and then axotomized by intraorbital optic nerve transection. Iron(III) 2,17-bis-sulfonato-5,10,15-tris(pentafluorophenyl)corrole (Fe(tpfc)(SO3H)2) (Fe-corrole) was injected intravitreally. Longitudinal imaging of RGCs was performed and the number of surviving RGCs enumerated. There was significantly greater survival of labeled RGCs with Fe-corrole, but the degree of neuroprotection was relatively less than that predicted by their ability to scavenge superoxide-This implies an unexpected complexity in signaling of apoptosis by reactive oxygen species.