Shunyu Lu1,2, Xiaojie Wei3, Hongliang Zhang2, Zhenfeng Chen4, Juman Li2, Xiaohui Xu2, Qiuqiao Xie2, Lixiu Chen2, Fangxing Ye2, Hoa Thi Thai Phama2, Luhui Jiang2, Tianmin Huang2, Jinbin Wei5, Renbin Huang6. 1. Department of Pharmacy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China. 2. Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People's Republic of China. 3. Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, 530000, People's Republic of China. 4. State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004, People's Republic of China. 5. Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People's Republic of China. jbwei@sina.cn. 6. Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People's Republic of China. huangrenbin518@163.com.
Abstract
BACKGROUND AND PURPOSE: Aβ1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aβ1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis. EXPERIMENTAL APPROACH: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aβ1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis. KEY RESULTS: Three concentration of DMDD (5 μmol/L, 10 μmol/L, and 20 μmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aβ1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aβ1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aβ1-42, but, which was suppressed by treated with DMDD. CONCLUSION AND IMPLICATIONS: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aβ1-42 through reversing the Bcl-2/Bax ratio.
BACKGROUND AND PURPOSE: Aβ1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aβ1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis. EXPERIMENTAL APPROACH: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aβ1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis. KEY RESULTS: Three concentration of DMDD (5 μmol/L, 10 μmol/L, and 20 μmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aβ1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aβ1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aβ1-42, but, which was suppressed by treated with DMDD. CONCLUSION AND IMPLICATIONS: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aβ1-42 through reversing the Bcl-2/Bax ratio.
Authors: Tomomi Kuwana; Lisa Bouchier-Hayes; Jerry E Chipuk; Christine Bonzon; Barbara A Sullivan; Douglas R Green; Donald D Newmeyer Journal: Mol Cell Date: 2005-02-18 Impact factor: 17.970
Authors: Lin Chen; Simon N Willis; Andrew Wei; Brian J Smith; Jamie I Fletcher; Mark G Hinds; Peter M Colman; Catherine L Day; Jerry M Adams; David C S Huang Journal: Mol Cell Date: 2005-02-04 Impact factor: 17.970