title: The role of charged multivesicular body protein 5 in programmed cell death in leukemic cells.
abstract: The Homo sapiens charged multivesicular body protein 5 (CHMP5) is a member of the multivesicular body, which serves as an anti-apoptotic protein and is thought to participate in leukemogenesis. In this study, a short-hairpin RNA-based RNA interference approach was used to inhibit the expression of CHMP5 in the leukemic cell line U937. After CHMP5 was inhibited, antibody microarray and western blot analysis were used to study the changes in the programmed cell death (PCD) pathway. PCD can be classified into three types: apoptosis, necrosis, and autophagy. Results showed that caspase 3 was activated in CHMP5-deficient U937 cells, indicating that the apoptotic pathway was activated, although neither the intrinsic nor the extrinsic apoptotic pathways were activated. Our results also showed that the Granzyme B/Perforin apoptotic pathway was activated by CHMP5 silencing. Necrosis is activated by caspase-independent executioners. In this study, we showed that the apoptosis-inducing protein-mediated necrotic PCD pathway is activated after CHMP5 inhibition. It was found that autophagic PCD did not occur in CHMP5-deficient U937 cells. In conclusion, after CHMP5 inhibition, both Granzyme B/Perforin apoptotic pathway and apoptosis-inducing factor-mediated necrotic pathway were activated, while autophagic pathway was not activated.
authors.affiliation: Emergency Department, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Feilong
authors.initials: F
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xiao
authors.forename: Renrong
authors.initials: R
authors.lastname: Ouyang
authors.forename: Aihua
authors.initials: A
authors.lastname: Fei
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Shen
authors.forename: Shuming
authors.initials: S
authors.lastname: Pan
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D009336:Necrosis; D054353:Perforin / Q000378:metabolism; D034622:RNA Interference; D020298:U937 Cells
chemical_list: D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; C499838:CHMP5 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D054353:Perforin; D053804:Granzymes; D053148:Caspase 3