Author(s): Li, YC (Li, Yu-Ching); Lin, HJ (Lin, Hui-Ju); Yang, JH (Yang, Jen-Hung); Yang, JS (Yang, Jai-Sing); Ho, HC (Ho, Heng-Chien); Chang, SJ (Chang, Shu-Jen); Hsai, TC (Hsai, Te- Chun); Lu, HF (Lu, Hsu-Feng); Huang, AC (Huang, An-Cheng); Chung, JG (Chung, Jing- Gung)
Title: Baicalein-Induced Apoptosis via Endoplasmic Reticulum Stress Through Elevations of Reactive Oxygen Species and Mitochondria Dependent Pathway in Mouse-Rat Hybrid Retina Ganglion Cells (N18)
Source: NEUROCHEMICAL RESEARCH, 34 (3): 418-429 MAR 2009 Language: English
Document Type: Article
Author Keywords: Baicalein; Reactive oxygen species (ROS); Cytochrome c; Cytoplasmic Ca2+; Caspase-3; Mitochondrial death pathway; 1,2-Bis(2-aminophenoxy) ethane-N,N,N ',N '- tetraacetic acid (BAPTA); Apoptosis
KeyWords Plus: SCUTELLARIA-BAICALENSIS; CANCER CELLS; 12-LIPOXYGENASE INHIBITION; GLUTATHIONE DEPLETION; OXIDATIVE STRESS; LEUKEMIA-CELLS;
ANNEXIN-V; DYSFUNCTION; MECHANISMS; FLAVONOIDS
Abstract: Studies were designed to investigate the effects of baicalein on mouse-rat hybrid retina ganglion cells (N18) to better understand its effect on apoptosis and apoptosis-related genes in vitro. Cell viability, reactive oxygen species (ROS), cytoplasmic Ca2+, mitochondrial membrane potential (MMP), apoptosis induction, and caspases-3 activity were examined by flow cytometric assay. Apoptosis-associated proteins such as p53, Bax, Bcl-2, cytochrome c, and caspase-3 were examined by Western blot. We demonstrated the increase in the levels of p53, Bax, and cytochrome c and decrease in the level of Bcl-2, which are associated with the induction of apoptotic cell death after 24 h treatment with baicalein in N18 cells. Baicalein induced an increase in the cytoplasmic levels of ROS and Ca2+ in 1 h and reached their peak at 3 h, and thereafter a loss of MMP by flow cytometry. We also demonstrated a release of the cytochrome c from mitochondria into cytosol and an activation of caspase-3, which led to the occurrence of apoptosis in N18 cells treated with baicalein by Western blot. Pretreatment was conducted with BAPTA (intracellular calcium chelator) in baicalein-treated cells, the decline of MMP was recovered, and the increase in the level of cytoplasmic Ca2+ was suppressed, and the proportion of apoptosis was also markedly diminished. In conclusion, our data suggests that oxidative stress and cellular Ca2+ modulates the baicalein-induced cell death via a Ca2+- dependent mitochondrial death pathway in N18 cells.
Addresses: [Chung, Jing-Gung] China Med Univ, Dept Microbiol, Sch Med, Taichung 404, Taiwan; [Lin, Hui-Ju] China Med Univ Hosp, Dept Ophthalmol, Taichung, Taiwan; [Yang, Jen- Hung] Chung Shan Med Univ Hosp, Dept Dermatol, Taichung, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung, Taiwan; [Ho, Heng-Chien] China Med Univ, Dept
Biochem, Taichung, Taiwan; [Chang, Shu-Jen] China Med Univ, Sch Chinese Med, Taichung, Taiwan; [Hsai, Te-Chun] China Med Univ Hosp, Dept Internal Med, Taichung, Taiwan; [Lu, Hsu-Feng] Cheng Hsin Rehabil Med Ctr, Dept Clin Pathol, Taipei, Taiwan; [Huang, An-Cheng]
Yuan Lin Kuo Hosp, Dept Pharm, Yuanlin Town, Changhua County, Taiwan; [Chung, Jing- Gung] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Wufeng, Taichung County, Taiwan; [Li, Yu-Ching] Cent Taiwan Univ Sci & Technol, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan
Reprint Address: Chung, JG, China Med Univ, Dept Microbiol, Sch Med, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected]
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Publisher: SPRINGER/PLENUM PUBLISHERS
Publisher Address: 233 SPRING ST, NEW YORK, NY 10013 USA ISSN: 0364-3190
DOI: 10.1007/s11064-008-9799-1
29-char Source Abbrev.: NEUROCHEM RES ISO Source Abbrev.: Neurochem. Res.
Source Item Page Count: 12
Subject Category: Biochemistry & Molecular Biology; Neurosciences ISI Document Delivery No.: 404JQ
