the activity of SOD and GSH-PX, and decreased the content of MDA in heart, liver and brain treated with D-galactose. Chrysanthemum also enhanced telo- merase activity of heart in aging mice. So chrysanthemum had the anti-aging ability. The mechanism might be via regulation of free radical metabolism, en- hancement of antioxidative enzyme and telomerase activities, and alleviation of lipid peroxide level. POLYPEPTIDES EXTRACT OF ACHYRANTHES Bidentata Blume PROTECTS AGAINST NMDA-INDUCED APOPTOSIS IN RAT CULTURED HIPPOCAMPAL NEURONS Hong Mei Shen 1,2 , Ying Yuan 1 , Fei Ding 1 , Xiao Song Gu 1 1 The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China 2 Institute of Nautical Medicine, Nantong University, Nantong, China Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS), and produces a marked effect by interacting with its receptors. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is known to play a pivotal role in triggering excitotoxicity. Overstimulation of NMDA receptors results in a significant increase of the intracellular Ca 2+ level followed by neuronal cell death, especially apoptosis. In contrast, NMDA re- ceptor antagonists are known to rescue neuronal cell death. Therefore seeking a natural bioactive substance, which can block NMDA receptors, becomes a hotspot of Chinese crude drug’s research. Achyranthes Bidentata Blume is a traditional Chinese medicine, which has been collected in Pharmacopoeia of the PRC. Polypeptides were extracted from the water-solution of Achyr- anthes Bidentata Blume. At the same time NMDA excitatory neurotoxicity model was developed in rat cultured hippocampal neurons. Using MTT assay, Hoechst/PI double staining and DNA ladder detection, our results indicated that the polypeptides had protective effect on neuronal cell death, especially apoptosis. Moreover, our data demonstrated that the protection was probably related to NMDA receptors by Ca 2+ image and whole-cell NMDA-evoked currents. POTASSIUM CHANNELS WERE INVOLVED IN ZINC- INDUCED APOPTOSIS IN MES23.5 CELLS Li Min Shi, Hong Jiang, Jun Wang, Ze Gang Ma, Jun Xia Xie Department of Physiology, Medical College of Qingdao University, Qingdao, China Previous researches have demonstrated that zinc may be involved in the pathogenesis of Parkinson’s disease by apoptotic pathway. However, the mechanisms underlying zinc-induced apoptosis are unknown. Previous stud- ies showed that 6-hydroxxydopamine (6-OHDA)-enhanced potassium chan- nels were involved in the apoptosis of dopaminergic neurons. Our study is to illustrate whether zinc-induced apoptosis was also mediated by potassium channels. First we demonstrated cell apoptosis with zinc treatment by hoechst staining assay. The results showed that 13.4 Æ 0.6% of MES23.5 cells were apoptotic after 24 h incubating with 60 mM zinc sulfate. Then we observed that the tyrosine hydroxylase (TH) mRNA expression and the dopamine content were decreased detected by semi-quantitative RT-PCR and high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Further study was conducted to elucidate the mechanism of cell apoptosis using whole-cell patch clamp recording. The data demon- strated that MES23.5 cells exhibited a tetraethylammonium (TEA)-sensitive outward K + current with delayed rectifier characteristics. Increases of K + current density were recorded following the treatment by 60 mM zinc for 2 - 8 hours. After incubation with 20 mM TEA, the zinc-induced enhance- ment of K + currents were fully blocked. Furthermore, incubation with TEA also could block zinc-mediated caspase-3 activation and cell apoptosis. These data suggest that zinc-induced apoptosis on MES23.5 dopaminergic cells may be due to the enhancement of TEA-sensitive K + channel activity. This work was supported by the grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2007CB516701, 2006CB500704) and the National Foundation of Natural Science of China (No. 30570649). IRON REGULATORY PROTEINS WERE INVOLVED IN THE 6-HYDROXYDOPAMINE (6-OHDA) INDUCED FERROPORTIN1 DOWN-REGULATION Ning Song, Jun Wang, Hong Jiang, Jun Xia Xie Department of Physiology, Medical College of Qingdao University, Qingdao, China Based on our previous study, we proposed that ferroportin1 (FP1) might ac- count for the nigral iron accumulation in 6-hydroxydopamine (6-OHDA) le- sioned Parkinson’s disease models. In the present study we observed the effect of 6-OHDA on iron efflux, as well as FP1 expression, in ventral mesen- cephalic neurons, cultured astrocytes and MES23.5 cells. The findings showed that 6-OHDA (10 mmol/L) decreased the iron efflux in these cells with de- creased mRNA and protein expressions of FP1. To further clarify that the down-regulation of FP1 was not due to the increased intracellular iron, these cells were overloaded with ferric ammonium citrate. Under iron overload con- ditions, FP1 showed a dose-dependent up-regulation. 6-OHDA treatment could increase both iron regulatory protein 1 (IRP1) and IRP2 mRNA expression. Silencing of IRPs by small interfering RNA dramatically abolished 6- OHDA-induced FP1 down-regulation. These results suggest that decreased ex- pression of FP1 was responsible for the decreased iron efflux with 6-OHDA treatment in ventral mesencephalic neurons, cultured astrocytes and MES23.5 cells. Down-regulation of FP1 by 6-OHDA was in an IRE/IRP-de- pendent manner. This work was supported by the grants from the National Pro- gram of Basic Research sponsored by the Ministry of Science and Technology of China (2007CB516701, 2006CB500704) and the National Foundation of Natural Science of China (No. 30600190 and 30570649). TRICHOSTATIN A INDUCES APOPTOSIS AND PROMOTES NEUROTOXIC EFFECTS OF NEUROTOXINS ON DOPAMINERGIC NEURONAL CELLS Yong Wang, Jin Hu, Xiao Ming Wang Key Laboratory for Neurodegenerative Disease of the Ministry of Education (China) and Department of Physiology, Capital Medical University, Beijing 100069, China Parkinson’s disease (PD) is a progressive neurodegenerative disease related to age, and primarily resulted from the death of dopaminergic neurons in the sub- stantia nigra. Increasing evidences have shown that epigenetic factors play im- portant roles in the aging and disorder of human being and animals. Trichostatin A (TSA) as a histone acetylation inhibitor was usually used to in- duce status alteration of histone acetylation in cells. In our studies, SH-SY5Y cells (human), N27 cells (rat) and MN9D (mouse) were used as cell models of dopaminergic neurons treated with TSA. Our results showed that treatment with TSA led to decreased cell viability and apoptosis in dopaminergic neuro- nal cells. Combination of TSA and typical neurotoxins in PD, i.e. MPP+, 6- OHDA or rotenone, resulted in stronger damages in dopaminergic neuronal cells than either of them. These results suggest that epigenetic regulation might play roles in pathogenesis of Parkinson’s disease through association with cell death of dopaminergic neurons. b-SECRETASE-1 (BACE1) EXPRESSION IN CEREBRAL NEOCORTEX SHOWS A MODULAR DISTRIBUTION PATTERN: INVERSE CORRELATION WITH ENDOGENOUS NEURONAL ACTIVITY Kun Xiong 1,2 , Ya Ping Chu 3 , Richard W. Clough 2 , Huai Bin Cai 4 , Xue Gang Luo 1 , Robert G. Struble 5 , Jeffrey H. Kordower 3 , Xiao Xin Yan 2 1 Department of Anatomy and Neurobiology, Central South University Xiangya Medical School, Changsha, Hunan, China, 410078 2 Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA, 62901 3 Department of Neurological Science, Rush University Medical Center, Chicago, IL, USA, 60612 4 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA, 20892 S10 Abstracts / Cell Biology International 32 (2008) S1eS67