Role of eukaryotic translation initiation factor 4G in tumor / 生理学报

Eukaryotic translation initiation factor 4G (eIF4G) is a scaffold component of eukaryotic translation initiation factor 4F (eIF4F) complex, which takes principal part in the initiating of protein synthesis. Both two subtypes (eIF4G1 and eIF4G2) of eIF4G were found to be closely related with various tumors. The eIF4G1 expression is significantly up-regulated in breast cancer, cervical cancer, nasopharyngeal carcinoma, lung squamous cell carcinoma, prostatic carcinoma and other malignant tumors, compared with those in adjacent tissues; and the eIF4G2 is obviously over-expressed in diffuse large B cell lymphoma and acute myeloid leukemia, but low-expressed in bladder transitional cell carcinoma. This paper reviews the progress in the study of the role of eIF4G in tumor genesis, development, diagnosis and prognosis.

Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway / 生理学报

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.

Design of antisense oligodeoxynucleotide targeting at bcl-2 mRNA and observation on its effect on the sensitivity of leukemia cells to arabinosyl cytosine / 中国实验血液学杂志

The effective target sites for antisense oligodeoxynucleotides (AS-ODN) on bcl-2 mRNA, except its start region, were looked for and their effects on the sensitivity of HL-60 and K562 leukemia cells to arabinosyl cytosine (Ara-C) were observed. The secondary structure of bcl-2 mRNA was simulated with RNAstructure microsoftware, and AS-ODNs, targeting at some sites, were designed and synthesizd with phosphorothioate modifying. The median inhibitory concentration (IC(50)) of Ara-C for HL-60 and K562 cells was determined with MTT method; the apoptosis rate and bcl-2 protein expression level were assayed by flow cytometry. The results showed that 10 micro mol/L bcl-2 AS-ODN combined with Ara-C inhibited the expression of bcl-2 protein, increased apoptosis in HL-60 and K562 cells and decresed IC(50) of Ara-C significantly. The AS-ODN targeting the coding region of bcl-2 mRNA had stronger effect than AS-ODN targeting the translation initiation region. In conclusion, the much more effective sites for antisense oligodeoxynucleotides to target, except translation start region, might provide a new useful way for antisense drug design.