6-羟基多巴胺诱导PC12细胞释放谷氨酸及死亡不受Ⅰ组亲代谢型谷氨酸受体配基的影响(英文)

目的:探讨Ⅰ组亲代谢型谷氨酸受体(mGluR)配基对6-羟基多巴胺(6-OHDA)诱导的PC12细胞死亡及谷氨酸(Glu)释放的影响。方法:培养PC12细胞,以100μmol/LⅠ组mGluR激动剂(RS)-3,5-dihydroxyphenylglycine(DHPG)和拮抗剂DL-2-amino-3-phosphonopropionic acid(DL-AP3)预先剌激细胞1h,再加入6-OHDA100μmol/L共孵育24h,显微镜下观察细胞形态变化,用TUNEL法检测凋亡细胞,用噻唑蓝(MTT)法检测细胞存活率,并用高效液相色谱检测Glu的释放量。结果:6-OHDA 降低PC12细胞存活率(P<0.01),其诱导的Glu释放呈浓度和时间依赖性。Ⅰ组mGluR配基不能减少6-OHDA引起的PC12细胞死亡,也不影响6OHDA引起的Glu释放量。结论:Ⅰ组mGluR配基对6-OHDA引起死亡的PC12细胞无保护作用。

Group I mGluR ligands fail to affect 6-hydroxydopamine- induced death and glutamate release of PC12 cells

AIM: To study the effect of group I metabotropic glutamate receptor (mGluR) ligands on 6-hydroxydopamine (6-OHDA)-induced death and glutamate release of PC12 cells. METHODS: PC12 cells were exposed to 100 micromol/L of group I mGluR agonist (RS)-3,5-dihydroxy-phenylglycine (DHPG) or antagonist DL-2-amino-3-phosphonopropionic acid (DL-AP3) 1 h before addition of 6-OHDA 100 micromol/L. After incubation for 24 h, morphological alterations were observed with microscope, DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, cytotoxicity was measured by MTT assay, and glutamate release was assayed by high performance liquid chromatography. RESULTS: 6-OHDA decreased cell viability (P<0.01) and induced concentration- and time-dependent glutamate release from PC12 cells. Group I mGluR ligands did not affect 6-OHDA-induced death of PC12 cells and had no influence on glutamate levels. CONCLUSION: Group I mGluR ligands cannot protect PC12 cells from 6-OHDA-induced death.