title: Beclin 1, an autophagy-related gene, augments apoptosis in U87 glioblastoma cells.
abstract: Beclin 1 acts as a tumor suppressor and is an essential mediator of autophagy. Beclin 1 also interacts with Bcl-2 and can induce apoptosis by activating the mitochondrion permeabilizing function of proapoptotic multidomain proteins from the Bcl-2 family. Moreover, these Bcl-2 family members can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-XL at the level of the endoplasmic reticulum. We found that overexpression of Beclin 1 in U87 glioblastoma cells enhanced the capacity for cellular autophagy and induced apoptosis. Silencing of Beclin 1 decreased autophagic capacity but had little effect on apoptosis and cell proliferation. Beclin 1-Bcl-2 and Beclin 1-Bcl-xL complexes were detected by immunoprecipitation in cells that overexpressed Beclin 1. Furthermore, the levels of cytochrome c in the cytosol and the activity of caspases-3/-9 in the cytosol increased after overexpression of Beclin 1. Our results suggest that Beclin 1 induces apoptosis via binding to Bcl-2 and Bcl-xL, followed by the release of cytochrome c into the cytosol and activation of caspases-3/-9.
authors.affiliation: Department of Neurosurgery, 171 Hospital, Jiujiang, Jiangxi 33200, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Qiangqian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Shiting
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D034741:RNA, Small Interfering