Background Ischemia/reperfusion injury （IRI） is an inflammatory response that occurs when tissue is reperfused following a prolonged period of ischemia. Several studies have indicated that C-reactive protein （CRP）...Background Ischemia/reperfusion injury （IRI） is an inflammatory response that occurs when tissue is reperfused following a prolonged period of ischemia. Several studies have indicated that C-reactive protein （CRP） might play an important role in inducing IRI. However, the effects of CRP on myocardial IRI and the underlying mechanisms have not been fully elucidated. This study aimed to investigate the association between CRP and myocardial IRI and the underlying mechanisms. Methods We simulated ischemia/reperfusion using oxygen-glucose deprivation/ reoxygenation （OGD/R） in neonatal Sprague-Dawley rat cardiomyocytes; reperfusion injury was induced by three hours of hypoxia with glucose and serum deprivation followed by one hour of reperfusion. Cell viability was tested with MTS assays, and cardiomyocyte damage was evaluated by lactate dehydrogenase （LDH） leakage. Mitochondrial membrane potential was measured using tetramethylrhodamine ethyl ester （TMRE） and mitochondrial permeability transition pore （mPTP） opening was measured using calcein/AM; both TMRE and caocein/AM were visualized with laser scanning confocal microscopy. In addition, we studied the signaling pathways underlying CRP-mediated ischemia/reperfusion injury via Western blot analysis. Results Compared with the simple OGD/R group, after intervention with 10 pg/mL CRP, cell viability decreased markedly （82.36 % ± 6.18% vs. 64.84% ± 4.06%, P = 0.0007）, and the LDH leakage significantly increased （145.3 U/L ± 16.06 U/L vs. 208.2 U/L ± 19.23 U/L, P = 0.0122）. CRP also activated mPTP opening and reduced mitochondrial membrane potential during myocardial ischemia/reperfusion. Pretreatment with 1 pM atorvastatin （Ator） before CRP intervention protected cardiomyocytes from IRI. Mitochondrial KATP channel opener diazoxide and mPTP inhibitor cyclosporin A also offset the effects of CRP in this process. The level of phosphorylated extracellular-signal-regulated kinase （ERK） 1/2 was significantly higher after pre-treatment with CRP compared with the OGD/R group （170.4% ± 3.00% v.v. 93.53% ± 1.94%, P 〈 0.0001）. Western blot analysis revealed that Akt expression was markedly activated （184.2% ± 6.96% vs. 122.7% ± 5.30%, P = 0.0003） and ERK 1/2 phosphorylation significantly reduced after co-treatment with Ator and CRP compared with the level after CRP pretreatment alone. Conclusions Our results suggested that CRP directly aggravates myocardial IRI in myocardial cells and that this effect is primarily mediated by inhibiting mitochondrial ATP- sensitive potassium （mitoKATp） channels and promoting mPTP opening. Ator counteracts these effects and can reduce CRP-induced IRI. One of the mechanisms of CRP-induced IRI may be related to the sustained activation of the ERK signaling pathway.展开更多
A wide range of host cellular signal transduction pathways can be stimulated by influenza virus infection. Some of these signal transduction pathways induce the host cell's innate immune response against influenza...A wide range of host cellular signal transduction pathways can be stimulated by influenza virus infection. Some of these signal transduction pathways induce the host cell's innate immune response against influenza virus, while others are essential for efficient influenza virus replication. This review examines the cellular signaling induced by influenza virus infection in host cells, including host pattern recognition receptor (PRR)-related signaling, protein kinase C (PKC), Raf/MEK/ERK and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and the corresponding effects on the host cell and/or virus, such as recognition of virus by the host cell, viral absorption and entry, viral ribonucleoprotein (vRNP) export, translation control of cellular and viral proteins, and virus-induced cell apoptosis. Research into influenza virus-induced cell signaling promotes a clearer understanding of influenza virus-host interactions and assists in the identification of novel antiviral targets and antiviral strategies.展开更多
Objective： Mitogen-activated protein kinases （MAPKs） are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 ...Objective： Mitogen-activated protein kinases （MAPKs） are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 （MKP-1） and phosphorylated extracellular signal-regulated kinase 1/2 （p-ERKl/2）, as the key regulatory mechanism of the MAPKs, in lung squamous cell carcinoma （SCC）. Methods： We assessed the expressions of MKP-1 and p-ERK1/2 in twenty subjects at different differentiation degree of SCC and five normal lungs by immunohistochemistry and real-time reverse transcriptase polymerase chain reaction （RT-PCR） analysis. Results： Immunohistochemistry and real-time RT-PCR assay showed that the expression of MKP-1 was gradually decreased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was negatively correlated with tumor differentiation （P〈0.01）. However, the expression of p-ERK1/2 or ERKl/2 was gradually increased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was positively correlated with tumor differentiation （P〈0.01）. Conclusions： Our data indicates the relevance of MKP-1 and p-ERK1/2 in SCC as a potential positive and negative prognostic factor. The imbalanced expression of MKP-1 and p-ERKl/2 may play a role in the development of SCC and these two molecules may be new targets for the therapy and prognosis of SCC.展开更多
文摘Background Ischemia/reperfusion injury （IRI） is an inflammatory response that occurs when tissue is reperfused following a prolonged period of ischemia. Several studies have indicated that C-reactive protein （CRP） might play an important role in inducing IRI. However, the effects of CRP on myocardial IRI and the underlying mechanisms have not been fully elucidated. This study aimed to investigate the association between CRP and myocardial IRI and the underlying mechanisms. Methods We simulated ischemia/reperfusion using oxygen-glucose deprivation/ reoxygenation （OGD/R） in neonatal Sprague-Dawley rat cardiomyocytes; reperfusion injury was induced by three hours of hypoxia with glucose and serum deprivation followed by one hour of reperfusion. Cell viability was tested with MTS assays, and cardiomyocyte damage was evaluated by lactate dehydrogenase （LDH） leakage. Mitochondrial membrane potential was measured using tetramethylrhodamine ethyl ester （TMRE） and mitochondrial permeability transition pore （mPTP） opening was measured using calcein/AM; both TMRE and caocein/AM were visualized with laser scanning confocal microscopy. In addition, we studied the signaling pathways underlying CRP-mediated ischemia/reperfusion injury via Western blot analysis. Results Compared with the simple OGD/R group, after intervention with 10 pg/mL CRP, cell viability decreased markedly （82.36 % ± 6.18% vs. 64.84% ± 4.06%, P = 0.0007）, and the LDH leakage significantly increased （145.3 U/L ± 16.06 U/L vs. 208.2 U/L ± 19.23 U/L, P = 0.0122）. CRP also activated mPTP opening and reduced mitochondrial membrane potential during myocardial ischemia/reperfusion. Pretreatment with 1 pM atorvastatin （Ator） before CRP intervention protected cardiomyocytes from IRI. Mitochondrial KATP channel opener diazoxide and mPTP inhibitor cyclosporin A also offset the effects of CRP in this process. The level of phosphorylated extracellular-signal-regulated kinase （ERK） 1/2 was significantly higher after pre-treatment with CRP compared with the OGD/R group （170.4% ± 3.00% v.v. 93.53% ± 1.94%, P 〈 0.0001）. Western blot analysis revealed that Akt expression was markedly activated （184.2% ± 6.96% vs. 122.7% ± 5.30%, P = 0.0003） and ERK 1/2 phosphorylation significantly reduced after co-treatment with Ator and CRP compared with the level after CRP pretreatment alone. Conclusions Our results suggested that CRP directly aggravates myocardial IRI in myocardial cells and that this effect is primarily mediated by inhibiting mitochondrial ATP- sensitive potassium （mitoKATp） channels and promoting mPTP opening. Ator counteracts these effects and can reduce CRP-induced IRI. One of the mechanisms of CRP-induced IRI may be related to the sustained activation of the ERK signaling pathway.
文摘A wide range of host cellular signal transduction pathways can be stimulated by influenza virus infection. Some of these signal transduction pathways induce the host cell's innate immune response against influenza virus, while others are essential for efficient influenza virus replication. This review examines the cellular signaling induced by influenza virus infection in host cells, including host pattern recognition receptor (PRR)-related signaling, protein kinase C (PKC), Raf/MEK/ERK and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and the corresponding effects on the host cell and/or virus, such as recognition of virus by the host cell, viral absorption and entry, viral ribonucleoprotein (vRNP) export, translation control of cellular and viral proteins, and virus-induced cell apoptosis. Research into influenza virus-induced cell signaling promotes a clearer understanding of influenza virus-host interactions and assists in the identification of novel antiviral targets and antiviral strategies.
基金supported by the National Natural Science Foundation of China (No. 30900654)the Science and Technology Department of Zhejiang Province (No. 2009R10031)the Health Bureau of Zhejiang Province (No. 2009QN010), China
文摘Objective： Mitogen-activated protein kinases （MAPKs） are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 （MKP-1） and phosphorylated extracellular signal-regulated kinase 1/2 （p-ERKl/2）, as the key regulatory mechanism of the MAPKs, in lung squamous cell carcinoma （SCC）. Methods： We assessed the expressions of MKP-1 and p-ERK1/2 in twenty subjects at different differentiation degree of SCC and five normal lungs by immunohistochemistry and real-time reverse transcriptase polymerase chain reaction （RT-PCR） analysis. Results： Immunohistochemistry and real-time RT-PCR assay showed that the expression of MKP-1 was gradually decreased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was negatively correlated with tumor differentiation （P〈0.01）. However, the expression of p-ERK1/2 or ERKl/2 was gradually increased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was positively correlated with tumor differentiation （P〈0.01）. Conclusions： Our data indicates the relevance of MKP-1 and p-ERK1/2 in SCC as a potential positive and negative prognostic factor. The imbalanced expression of MKP-1 and p-ERKl/2 may play a role in the development of SCC and these two molecules may be new targets for the therapy and prognosis of SCC.
