1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells.

Hyun Park,Jong Kang,Myung Lee

doi:10.3390/molecules24050867

Abstract

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on l-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both l-DOPA-induced cell death and superoxide dismutase activity reduction. When assessing the effect of HTHQ on oxidative stress-related signaling pathways, HTHQ inhibited l-DOPA-induced phosphorylation of sustained extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1/2). HTHQ also normalized l-DOPA-reduced Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression, promoting cell survival. Taken together, HTHQ exhibits protective effects against l-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. These results suggest that HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, although further studies in animal models of Parkinson’s disease are required to confirm this.

Highlights

National University, 194-21, Osongsaengmyung 1-ro, Osong, Heungduk-gu, Cheongju 28160, Korea; Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, 1, Academic Editor: Jia Zhou
In the cell-free condition, the addition of HTHQ to MTT solution did not cause the changes in the values of optical density, suggesting that HTHQ did not interact directly with MTT
Discussion compared to L-DOPA-treated group (200 μ M) (ANOVA with post-hoc Tukey’s test)

Summary

Introduction

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on L-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both L-DOPA-induced cell death and superoxide dismutase activity reduction. HTHQ exhibits protective effects against L-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, further studies in animal models of Parkinson’s disease are required to confirm this. 1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a hydroquinone monoalkyl ether, is a potent antioxidative agent that has been found to exert anti-lipid-peroxidative activity in rat liver microsomes [1] and chemopreventive effects against heterocyclic amine-induced carcinogenesis [2]

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