梓醇对 PC12 细胞多巴胺生物合成及 L-DOPA 诱导细胞毒性的影响。

Effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.

机构信息

College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.

出版信息

Environ Toxicol Pharmacol. 2008 Jul;26(1):86-91. doi: 10.1016/j.etap.2008.02.005. Epub 2008 Feb 17.

DOI:10.1016/j.etap.2008.02.005

Abstract

The effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalpalactone at 5-30μM decreased intracellular dopamine content with the IC(50) value of 22.1μM. Catalpalactone at 5-20μM, but not 30μM, did not alter cell viability. Catalpalactone at 20μM inhibited tyrosine hydroxylase (TH) and aromatic-l-amino acid decarboxylase (AADC) activities. Catalpalactone also decreased cyclic AMP levels and inhibited TH phosphorylation. In addition, catalpalactone at 20μM reduced the increases in dopamine levels induced by L-DOPA (20-50μM). Catalpalactone (5-30μM) associated with L-DOPA (50-100μM) enhanced L-DOPA-induced cytotoxicity at 48h, which was prevented by N-acetyl-l-cysteine. These results suggest that catalpalactone inhibited dopamine biosynthesis by reducing TH and AADC activities and enhanced L-DOPA-induced cytotoxiciy in PC12 cells.

摘要

研究了梓醇内酯对 PC12 细胞中多巴胺生物合成和 L-DOPA 诱导的细胞毒性的影响。梓醇内酯在 5-30μM 浓度下降低细胞内多巴胺含量，IC50 值为 22.1μM。梓醇内酯在 5-20μM 浓度下，但在 30μM 浓度下不改变细胞活力。梓醇内酯在 20μM 浓度下抑制酪氨酸羟化酶（TH）和芳香族-l-氨基酸脱羧酶（AADC）的活性。梓醇内酯还降低 cAMP 水平并抑制 TH 磷酸化。此外，梓醇内酯在 20μM 浓度下降低了 L-DOPA（20-50μM）诱导的多巴胺水平增加。梓醇内酯（5-30μM）与 L-DOPA（50-100μM）联合使用在 48 小时时增强了 L-DOPA 诱导的细胞毒性，这可以被 N-乙酰-l-半胱氨酸所预防。这些结果表明，梓醇内酯通过降低 TH 和 AADC 的活性抑制多巴胺生物合成，并增强 PC12 细胞中 L-DOPA 诱导的细胞毒性。