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

Hai Shan Huang; Xiang Hua Han; Bang Yeon Hwang; Jae In Park; Se Kuel Yoo; Hak Ju Lee; Sung Cil Lim; Myung Koo Lee

doi:10.1016/j.etap.2008.02.005

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

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

Authors

Hai Shan Huang¹, Xiang Hua Han, Bang Yeon Hwang, Jae In Park, Se Kuel Yoo, Hak Ju Lee, Sung Cil Lim, Myung Koo Lee

Affiliation

¹ College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.

PMID: 21783893
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.