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Injured neurons will send "help-me" signals to nearby cells after focal injuries. These neurons will be protected by proliferation of neural progenitors, transformation of microglia, and proliferation of endothelial cells. This article provides an in-depth review of the latest research on endogenous " helpme" signals after neuronal injury, especially after cerebral ischemia injury was made, suggesting findings of endogenous "help-me" signals after neuronal injury and its usage as a novel target for intervention may provide new ideas and methods for neuroprotection researches.
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Breast cancer is one of the most common malignant tumors in women, and its incidence has increased year by year, which is one of the most important causes of death among women, especially young women. Studying related cell signal transduction that affects the development and progression of breast cancer can help prevent the occurrence of breast cancer, slow down the cancer progression and improve the prognosis of patients. nitric oxide (NO) is a kind of signaling molecule. Many studies have shown that the production and expression of NO are closely related to breast cancer. NO-related cell signal transduction significantly affects the occurrence and development of breast cancer. However, the understanding of the relationship between NO and breast cancer associated cell signal transduction needs to be further improved. In this paper, the related studies on NO-related cellular signal transduction in breast cancer were reviewed with a view to improving the understanding of the development and progression of breast cancer.
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Aim To investigate the roles of FFJ-5 in human breast cancer MCF7 cells and drug-resistant MCF7/DOX cells and to explore its mechanisms. Methods MTT assay was used to detect the effect of FFJ-5 on MCF7 and MCF7/DOX cell proliferation and sensitivity of doxorubicin in MCF7/DOX cells.West-ern blot was used to investigate the effect of FFJ-5 on expression of EGFR,p-EGFR,Akt,p-Akt,PKM2, cleaved caspase-3,cleaved PARP and P-gp.DNA lad-der analysis was performed to determine the effect of FFJ-5 on genomic DNA.RT-PCR was performed to de-tect the influence of FFJ-5 on multidrug resistance gene MDR1 mRNA levels.Results The results showed that FFJ-5 inhibited the growth of MCF7 ,inhibited the expression and activity of EGFR and Akt,and conse-quently reduced the expression of PKM2 in MCF7 cells;FFJ-5 activated caspase-3 and induced genomic DNA fragmentation;FFJ-5 also inhibited the growth of MCF7/DOX cells and enhanced the anti-tumor activity of doxorubicin in MCF7/DOX cells.Conclusion The results suggest that FFJ-5 could inhibit MCF7 cell growth and induce MCF7 cell apoptosis through inhibi-tion of EGFR-Akt-PKM2 pathway and activation of ap-optosis-related factors caspase-3 , meanwhile FFJ-5 could also reverse the resistance of MCF7/DOX.
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Dact proteins belong to a structure-related protein family. Recent studies have demonstrated that Dact proteins play an important role in tumorigenesis via modulation of wnt and TGF-p signaling. Delin-eation of the physiological function of Dact proteins would enhance our understanding of look for new strategy targets for cancer and suggests a potential strategy for therapeutic control of wnt and TGF-β signaling in canc-er.
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Abnormal cell signal transduction is associated with the occurrence and development of human diseases. Some virus pathogenicity and infection mechanism are due to virus antigen protein acting on the host cell signal transduction pathway, leading to host cell signal transduction disorder. Hepatitis C virus (HCV) is a major pathogen of chronic hepatitis C, which causes cirrhosis and hepatocellular carcinoma. But the pathogenesis of HCV and persistent infection mechanism remain far from clear. HCV pathogenesis may be related to the HCV protein expression interfering host cell signal transduction pathways. The studies of hepatitis C virus proteins acting on host cell signal transduction pathways, not only help to clarify the impact of its pathogenic mechanisms, but also benefit to new drug design and development for new treatment methods. This article summarizes the recent progress in research on the effect of hepatitis C virus protein in cell signal transduction pathways in the past few years.
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Aim To investigate effects of Sevoflurane on PI_3-K/Akt/P~(70S6K) cell-survival signal transduction pathways after neuron ischemia-reperfusion,and explore neuroprotection mechanisms of sevoflurane.Methods Newborn(24～48 h)Wister rats were decapitated and hippocampus tissue was dissected and cut into 1 mm?1 mm?1 mm pieces.Then digestion with 0.125% trypsin,centrifuged at 800 r?min~(-1) for 5 min at 4℃,and suspended in a medium containing DMEM supplemented to 25 mmol?L~(-1) glucose,10% fetal bovine serum,10% horse serum,and 2 mmol?L~(-1) glutamine.Cells were plated at 1.0?10~5?ml~(-1) on poly-Dlysine-treated 96-well(100 ?l/well)plates as well 6-well(2 ml/well) plates.Cultures were treated with 10 ?mol?L~(-1) cytosine arabinoside on day 4 in culture to minimize glial growth.One-half of the medium was replaced twice a week with medium containing DMEM(4.5 g?L~(-1) glucose)/F12(1 ∶1),5% fetal bovine serum and 5% horse serum.Cells were used after 7 days. For ischemia-reperfusion(oxygen glucose deprivation,OGD)experiments,cultures were washed three times in a glucose-free balanced salt solution(BSS)and placed in deoxygenated glucose-free medium and sealed under 95% N_2-5% CO_2 in an anaerobic chamber equilibrated to 37℃ and 100% humidity for 45 min.OGD was terminated by replacement of stored medium and by returning the cultures to a standard incubator maintained at 37℃ in 95% O_2-5% CO_2.Experimental group cells were respectively carried out OGD,OGD+2% Sevoflurane,OGD+2% Sevoflurane +10 ?mol?L~(-1) LY294002,OGD+2% Sevoflurane +10 ?mol?L~(-1) Triciribin,and OGD+2% Sevoflurane +10 nmol?L~(-1) Rapamycin.Control cells were cultured normally.Group Sevo was carried out OGD meanwhile anesthesized with 2% sevoflurane.Group LY,Tri and Rap cells was carried out OGD meanwhile culture medium was added 10 ?mol?L~(-1) LY294002,10 ?mol?L~(-1) Triciribin or 10 nmol?L~(-1) Rapamycin,and anesthesized with 2% sevoflurane.Compound remained present throughout the duration of the experiment until analysis 24 h later.Neuron viability and apoptosis were measured.The protein expression of PI_3-K,Akt and P~(70S6K) were detected.Results Sevoflurane enhanced expression of PI_3-K,Akt and P~(70S6K),meanwhile increased neuron viability and decreased neuron apoptosis(vs group I/R,P
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BACKGROUND: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. METHOD: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNFalpha was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNFalpha antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. RESULTS: LPS alone did not increase significantly MUC5AC production. LPS with TGFalpha induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNFalpha secretion, which was inhibited by mastoparan. LPS with TGFalpha-induced MUC5AC production was inhibited by neutralizing polyclonal TNFalpha antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. CONCLUSION: In LPS-induced MUC5AC synthesis, LPS causes TNFalpha secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.
Subject(s)
Enzyme-Linked Immunosorbent Assay , Epidermal Growth Factor , GTP-Binding Proteins , Mucins , Mucus , Phosphorylation , Protein-Tyrosine Kinases , ErbB Receptors , Receptors, G-Protein-Coupled , Signal Transduction , Transcriptional Activation , Transforming Growth Factor alpha , Tumor Necrosis Factor-alphaABSTRACT
AIM: To explore the molecular mechanism in the pathogenesis of dilated cardiomyopathy (DCM) by analyzing the expression of T cell signaling molecules in mice with autoimmune DCM. METHODS: Mouse DCM model was induced by immunizing the animals with adenine nucleotide translocase (ANT) synthetic peptides. P56lck in T cells was detected with real-time fluorescent quantitative PCR in both DCM-group and the sham-immunized controls. At the same time, flow cytometry was used for quantity of Th cell intracellular cytokine IFN-? and IL-4, ELISA for examining the level of serum anti-ANT antibody, immune histochemistry for investigating the expression of CD45 in Th cells. RESULTS: The mRNA expression of P56lck ( 1 369.51 ?874.05 vs 47.93?10.21, P