title: [Molecular mechanism of beta cell apoptosis induced by p58 in high glucose medium].
abstract: Type 2 diabetes is a complex disorder with a strong genetic background. CDC2L2 is one of the susceptibility genes of type 2 diabetes in Chinese Han population in northern area. The relationship between CDC2L2 and type 2 diabetes remains unknown. In this paper, the function and its molecular pathway of p58, a protein coded by CDC2L2, in beta cell apoptosis were investigated. INS-1 cells cultured in high glucose (20 mmol/L) medium were divided into control, vector control (transfected with pcDNA3.0) and experimental (transfected with pcDNA3.0-HA-p58) groups. Beta cell apoptosis level was detected by Annexin V-FITC/PI double staining assay. The flow cytometry results showed that in high glucose medium (20 mmol/L), high expression of p58 increased beta cell apoptosis significantly compared with that in blank and vector controls (P<0.01, P<0.05). Western blot revealed that the expressions of Caspase-3, Bax and cytochrome C in cytoplasm increased significantly (P<0.05, P<0.01, P<0.01), whereas the expression of Bcl-2 decreased significantly (P<0.05) in the INS-1 cells with high expression of p58, compared with those in both control groups. However, the Bad and Bik expression levels of INS-1 cells did not show obviously changes compared with those in both controls. The above results suggest that in high glucose condition, p58 may induce INS-1 cell apoptosis through up-regulating the expression of Bax and down-regulating the expression of Bcl-2, since both of them could promote the release of cytochrome C into cytoplasm, and finally activate Caspase-3. These results provide an important basis for the further exploration of the molecular mechanism of beta cell apoptosis induced by CDC2L2.
authors.affiliation: Department of Physiology and Biomedical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong-Wang
authors.initials: HW
authors.lastname: Yang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2; D005947:Glucose / Q000737:chemistry; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D003470:Culture Media; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D005947:Glucose