Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retina
Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retina
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DOI：
10.1111/j.1471-4159.2006.03871.x
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发表时间：
2006-07-01
影响因子：
4.7
通讯作者：
Tanihara, Hidenobu
中科院分区：
文献类型：
--
作者：
Inomata, Yasuya;Nakamura, Hajime;Tanihara, Hidenobu
硫氧还蛋白（TRX）在生物体中起着多种氧化还原相关的作用。为了研究其作为内源性氧化还原调节剂在NMDA诱导的视网膜神经毒性中的作用，我们将NMDA与TRX、突变型TRX或生理盐水注射到大鼠眼玻璃体腔中。视网膜神经节细胞被拯救TRX，与生理盐水相比，在NMDA注射后7天通过逆行标记分析进行评价。TRX，但不是它的突变形式，防止NMDA诱导的视网膜细胞凋亡，测量末端脱氧核苷酸转移酶介导的UTP缺口末端标记。在TRX处理的眼睛中，NMDA对caspase 3和9的诱导显著低于盐水处理的眼睛，但对caspase 8的诱导不显著。NMDA诱导的MAPK，p38激酶和c-Jun N-末端激酶的激活后6小时和MAPK激酶（MKKs）MKK 3/6和MKK 4后3小时在视网膜神经节细胞中被TRX显着抑制，但不是由突变形式。NMDA诱导的蛋白质羰基化，亚硝基化和脂质过氧化的增加也被抑制在TRX治疗的眼睛。我们的结论是，玻璃体内注射TRX有效地衰减NMDA诱导的视网膜细胞损伤，抑制氧化应激和抑制凋亡信号通路参与这种神经保护。
Thioredoxin (TRX) plays a variety of redox-related roles in organisms. To investigate its function as an endogenous redox regulator in NMDA-induced retinal neurotoxicity, we injected NMDA with TRX, mutant TRX or saline into the vitreous cavity of rat eyes. Retinal ganglion cells were rescued by TRX, compared with saline, when evaluated by retrograde labeling analysis at 7 days after NMDA injection. TRX, but not its mutant form, prevented NMDA-induced apoptosis in the retina, as measured by terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling. The induction of caspase 3 and 9, but not caspase 8, by NMDA was significantly lower in TRX-treated eyes than in saline-treated eyes. NMDA-induced activation of the MAPKs, p38 kinase and c-Jun N-terminal kinase after 6 h and of the MAPK kinases (MKKs) MKK3/6 and MKK4 after 3 h was markedly suppressed in retinal ganglion cells by TRX but not by the mutant form. NMDA-induced increases in protein carbonylation, nitrosylation and lipid peroxidation were also suppressed in TRX-treated eyes. We concluded that the intravitreous injection of TRX effectively attenuated NMDA-induced retinal cell damage and that suppression of oxidative stress and inhibition of apoptotic signaling pathways were involved in this neuroprotection.