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KMID : 0620920070390030316
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Experimental & Molecular Medicine
2007 Volume.39 No. 3 p.316 ~ p.326
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Protective effects of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-hydroxydopamine-induced neuronal cell death
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Park Byung-Chul
Lee Yong-Soo
Park Hee-Juhn
Kwak Mi-Kyoung
Yoo Bong-Kyu
Kim Joo-Young
Kim Jung-Ae
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Abstract
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6-Hydroxydopamine (6-OHDA) is a neurotoxin and is commonly used to generate experimental models of Parkinson’s disease (PD). In this study, we investigated the signaling molecules involved in the 6- OHDA-induced cell death using a neuronal catecholaminergic cell line (SK-N-SH cells), and the protective effect of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-OHDA-induced neuronal death. 6-OHDA significantly increased levels of reactive oxygen species (ROS), intracellular Ca2+ ([Ca2+]i), and p38 phosphorylation. In addition, this ROS increase by 6-OHDA was reduced by pretreatment with N-acetylcysteine (NAC), a free radical scavenger, but not by bis-(o-aminophenoxy)- ethane-N,N,N,N- tetraacetic acid (BAPTA), a Ca2+ chelator. However, the [Ca2+]i increase induced by 6-OHDA was suppressed by NAC. Moreover, pretreatment with NAC or BAPTA significantly prevented the 6-OHDA- induced increases in p38 phosphorylation, Bax/ Bcl-2 ratio, and caspase-3 activity. Although 6- OHDA-increased phosphorylation of p38 was prevented by NAC or BAPTA, inhibition of p38 by SB203580 did not suppress ROS, Bax/Bcl-2 ratio, or caspase-3 activity increases, and only partially prevented 6-OHDA-induced cell death, thus demonstrating that p38 activation is a component of a signaling pathway leading to the initiation of 6-OHDA-induced cell death, which acts in parallel with an ROS-Ca2+-Bcl-2-caspase-3 pathway. Moreover, fustin not only suppressed 6-OHDA-induced cell death in a concentration-dependent manner but also blocked 6-OHDA-induced increases in ROS, [Ca2+]i, Bax/Bcl-2 ratio, caspase-3 activity, and p38 phosphorylation. These results suggest that fustin exerts neuroprotection against 6-OHDA-induced cell death.
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KEYWORD
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calcium, caspase-3, cell death, oxidopamine, p38 mitogen-activated protein kinases, Parkinson disease, reactive oxygen species
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