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Reactive oxygen species-induced apoptosis in PC12 cells and protective effect of bilobalide.
J Pharmacol Exp Ther. 2000 Jun; 293(3):982-8.JP

Abstract

Although clinical studies have demonstrated that EGb 761, a standard extract of Ginkgo biloba, was effective in mild-to-moderate dementia of the Alzheimer's disease patients, the mechanism underlying its neuroprotective effect remains unclear. In this study, effects of bilobalide, the main constituent of the nonflavone fraction of EGb 761, on reactive oxygen species (ROS)-induced apoptosis in PC12 cells was studied. Exposure of cells to xanthine (100 microM)/xanthine oxidase (150 mU/ml) (ROS producer) resulted in a characteristic DNA fragmentation and an increase in the apoptosis rate. When p53, c-Myc, Bcl-2, Bcl-x(L), and Bax were measured by flow cytometry and the activities of caspase-1- and caspase-3-like protease determined with Ac-YVAD-AMC or Ac-DEVD-AMC as substrates, the profile of ROS-induced changes in these apoptosis regulatory and effector proteins suggests that elevation of c-Myc, p53, and Bax and activation of caspase-3 play an important role in the apoptosis. When cells were treated with ROS and bilobalide (25-100 microM) simultaneously, a dose-dependent reduction in the apoptotic rate was found. The percentage of cells with positive staining for c-Myc and p53 decreased from 27.8 and 50.1% to 16.7 and 23.2%, respectively, when bilobalide (25 microM) was present. Bilobalide also reduced ROS-induced elevation of Bax and activation of caspase-3 effectively. Our results provide the first direct evidence that bilobalide can protect neurons against oxidative stress. Bilobalide may block the apoptosis in the early stage and then attenuate the elevation of c-Myc, p53, and Bax and activation of caspase-3 in cells.

Authors+Show Affiliations

Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10869401

Citation

Zhou, L J., and X Z. Zhu. "Reactive Oxygen Species-induced Apoptosis in PC12 Cells and Protective Effect of Bilobalide." The Journal of Pharmacology and Experimental Therapeutics, vol. 293, no. 3, 2000, pp. 982-8.
Zhou LJ, Zhu XZ. Reactive oxygen species-induced apoptosis in PC12 cells and protective effect of bilobalide. J Pharmacol Exp Ther. 2000;293(3):982-8.
Zhou, L. J., & Zhu, X. Z. (2000). Reactive oxygen species-induced apoptosis in PC12 cells and protective effect of bilobalide. The Journal of Pharmacology and Experimental Therapeutics, 293(3), 982-8.
Zhou LJ, Zhu XZ. Reactive Oxygen Species-induced Apoptosis in PC12 Cells and Protective Effect of Bilobalide. J Pharmacol Exp Ther. 2000;293(3):982-8. PubMed PMID: 10869401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reactive oxygen species-induced apoptosis in PC12 cells and protective effect of bilobalide. AU - Zhou,L J, AU - Zhu,X Z, PY - 2000/6/28/pubmed PY - 2000/7/25/medline PY - 2000/6/28/entrez SP - 982 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 293 IS - 3 N2 - Although clinical studies have demonstrated that EGb 761, a standard extract of Ginkgo biloba, was effective in mild-to-moderate dementia of the Alzheimer's disease patients, the mechanism underlying its neuroprotective effect remains unclear. In this study, effects of bilobalide, the main constituent of the nonflavone fraction of EGb 761, on reactive oxygen species (ROS)-induced apoptosis in PC12 cells was studied. Exposure of cells to xanthine (100 microM)/xanthine oxidase (150 mU/ml) (ROS producer) resulted in a characteristic DNA fragmentation and an increase in the apoptosis rate. When p53, c-Myc, Bcl-2, Bcl-x(L), and Bax were measured by flow cytometry and the activities of caspase-1- and caspase-3-like protease determined with Ac-YVAD-AMC or Ac-DEVD-AMC as substrates, the profile of ROS-induced changes in these apoptosis regulatory and effector proteins suggests that elevation of c-Myc, p53, and Bax and activation of caspase-3 play an important role in the apoptosis. When cells were treated with ROS and bilobalide (25-100 microM) simultaneously, a dose-dependent reduction in the apoptotic rate was found. The percentage of cells with positive staining for c-Myc and p53 decreased from 27.8 and 50.1% to 16.7 and 23.2%, respectively, when bilobalide (25 microM) was present. Bilobalide also reduced ROS-induced elevation of Bax and activation of caspase-3 effectively. Our results provide the first direct evidence that bilobalide can protect neurons against oxidative stress. Bilobalide may block the apoptosis in the early stage and then attenuate the elevation of c-Myc, p53, and Bax and activation of caspase-3 in cells. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10869401/Reactive_oxygen_species_induced_apoptosis_in_PC12_cells_and_protective_effect_of_bilobalide_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10869401 DB - PRIME DP - Unbound Medicine ER -