Inhibitory effects of constituents of Gastrodia elata Bl. on glutamate-induced apoptosis in IMR-32 human neuroblastoma cells.
The inhibitory effects of the constituents of Gastrodia elata Bl. (GE) on glutamate-induced apoptosis in human neuronal cells were investigated using IMR32 human neuroblastoma cells. Glutamate (GLU) induced DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. GLU also induced a slow and sustained increase in intracellular Ca2+ concentration. Treatment with EGTA, an extracellular Ca2+ chelator, in a nominal Ca2+-free buffer solution abolished the GLU-induced intracellular Ca2+ increase, indicating that GLU stimulated Ca2+ influx pathway in the IMR32 cells. BAPTA, an intracellular Ca2+ chelator, significantly inhibited the GLU-induced apoptosis assessed by the flow cytometry measuring hypodiploid DNA content indicative of apoptosis, implying that intracellular Ca2+ rise may mediate the apoptotic action of GLU. Vanillin (VAN) and p-hydroxybenzaldehyde (p-HB), known constituents of GE, significantly inhibited both intracellular Ca2+ rise and apoptosis induced by GLU. These results suggest that the apoptosis-inhibitory actions of the constituents of GE may account, at least in part, for the basis of their antiepileptic activities. These results further suggest that intracellular Ca2+ signaling pathway may be a molecular target of the constituents of GE.
Lee
Y S
YS
Department of Physiology, College of Medicine, Kwandong University, Kangnung, Korea.
Ha
J H
JH
Yong
C S
CS
Lee
D U
DU
Huh
K
K
Kang
Y S
YS
Lee
S H
SH
Jung
M W
MW
Kim
J A
JA
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D002614:Chelating Agents; D004273:DNA, Neoplasm; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D002118:Calcium