Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Protective effects of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-hydroxydopamine-induced neuronal cell death

Park, Byung-Chul;Lee, Yong-Soo;Park, Hee-Juhn;Kwak, Mi-Kyoung;Yoo, Bong-Kyu;Kim, Joo-Young;Kim, Jung-Ae

  • Published : 20070600
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Abstract

6-Hydroxydopamine (6-OHDA) is a neurotoxin and is commonly used to generate experimental models of Parkinsons disease (PD). In this study, we investi-gated the signaling molecules involved in the 6- OHDA-induced cell death using a neuronal cate-cholaminergic cell line (SK-N-SH cells), and the protective effect of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-OHDA-induced neuronal y increased levels of reac-tive oxygen species (ROS), intracelular 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 su-ppressed by NAC. Moreover, pretreatment with NAC or BAPTA significantly prevented the 6-OHDA- Bcl-2 ratio, and caspase-3 activity. Although 6- OHDA-increased phosphorylation of p38 was pre-vented 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 demon-strating 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. More-over, 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.

Keywords

References

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