Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G
Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G
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DOI：
10.1006/bbrc.2000.3160
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发表时间：
2000-08-11
影响因子：
3.1
通讯作者：
Bagetta, G
中科院分区：
文献类型：
--
作者：
Corasaniti, MT;Strongoli, MC;Bagetta, G
使用蛋白质印迹法和 ELISA 技术，将单剂量的 HIV-1 外壳蛋白 gp120 注射到一侧侧脑室 (i.c.v.) 对 2 型环氧合酶 (COX-2) 和 PGE 表达水平进行了研究，该技术应用于从个体大鼠的新皮质中获得的脑组织提取物，新皮质是病毒蛋白导致细胞凋亡的中枢神经系统区域之一。结果表明，单剂量 (100 ng) gp120 6 小时后，COX-2 表达几乎翻倍，同时 PGE 也有统计学显着升高。 COX-2 表达增强与 gp120 诱发的细胞凋亡机制有关，因为后者被 COX-2 活性的选择性抑制剂 NS398（10 mg/kg i.p.）所阻止。 NMDA 受体拮抗剂（例如 MK801（0.3 mg/kg 腹腔注射）和 CGP040116（10 mg/kg 腹腔注射）以及自由基清除剂 U-74389G（10 mg/kg 腹腔注射）也可提供保护，支持由 gp120 诱导的谷氨酸介导的兴奋性毒性细胞凋亡机制。这些数据以及 MK801 未能阻止 gp120 增强的 COX-2 表达的观察结果表明，花生四烯酸级联的产物可能是导致突触谷氨酸升高的原因，导致新皮质细胞氧化应激和兴奋性毒性细胞凋亡。 (C) 2000 年学术出版社。
The effects of a single dose of the HIV-1 coat protein gp120 given into one lateral cerebral ventricle (i.c.v.) on the expression of cyclooxygenase type 2 (COX-2) and PGE, levels have been studied using Western blotting and ELISA techniques applied to brain tissue extracts obtained from the neocortex of individual rats, one of the regions of the central nervous system where the viral protein causes apoptosis. The results demonstrate that COX-2 expression is almost doubled 6 h after a single dose (100 ng) of gp120 and this is paralleled by a statistically significant elevation of PGE,. Enhanced COX-2 expression is implicated in the mechanisms of apoptosis evoked by gp120 because the latter is prevented by NS398 (10 mg/kg i.p.), a selective inhibitor of COX-2 activity. Protection is also afforded by NMDA receptor antagonists, such as MK801 (0.3 mg/kg i.p.) and CGP040116 (10 mg/kg i.p.), and by the free radical scavenger, U-74389G (10 mg/kg i.p.), supporting a glutamate-mediated, excitotoxic, mechanism of apoptotic death induced by gp120. These data together with the observation that MK801 failed to prevent gp120-enhanced COX-2 expression indicate that products of the arachidonic cascade may be responsible for elevation of synaptic glutamate leading neocortical cells to oxidative stress and excitotoxic apoptosis. (C) 2000 Academic Press.