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

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

  • Molecules. 2019 Mar 1;24(5):867. doi: 10.3390/molecules24050867.
Hyun Jin Park 1 Jong Koo Kang 2 Myung Koo Lee 3
Affiliations

Affiliations

  • 1 Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 194-21, Osongsaengmyung 1-ro, Osong, Heungduk-gu, Cheongju 28160, Korea. bwind77@hanmail.net.
  • 2 Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Korea. jkkang@chungbuk.ac.kr.
  • 3 Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 194-21, Osongsaengmyung 1-ro, Osong, Heungduk-gu, Cheongju 28160, Korea. myklee@chungbuk.ac.kr.
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.

Keywords

1-O-hexyl-2,3,5-trimethylhydroquinone; ERK1/2; JNK1/2; PC12 cells; l-DOPA-induced cytotoxicity; superoxide dismutase.

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