ABSTRACT
Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.
ABSTRACT
As the second cause of cancer relative deaths,gastric cancer's different biological characteristics lead to obviously different treatment results and prognosis.The mechanism to determine the initiation,lead to obviously different development and the biological characreristics of gastric cancer is doctors' interest.Recently,platelet-de-rived growth factor receptor-β (PDGFR-β) become one of hot research fields,its excessive activation and abnormal expression can induce tumor angiogenesis,and promote tumor growth,and can also degrade extracellular matrix,reduce the number of cell adhesion molecular.Through these,PDGFR-β was directly or indirectly involved in tumor invasion and metastasis.PDZK1 can bind with PDGFR-β specifically and futher affect the downstream of PDGFR-β signaling pathway (Ras-MAPK signaling pathway,the PI3K-Akt signaling pathway,PLC signaling pathway),and then affect cell proliferation,differentiation and migration.