共查询到20条相似文献，搜索用时 15 毫秒
1.
AIM: To study the effect of targeting protein for Xenopus kinesin-like protein 2 (TPX2) expression knockdown on the apoptosis of rectal cancer HR-8348 cells.METHODS: The HR-8348 cells transfected with TPX2 small interfering RNA (siRNA) served as TPX2 siRNA group. The non-transfected cells were used as control group. The cells transfected with siRNA negative control (siRNA-NC) were used as siRNA-NC group. The TPX2 siRNA-transfected cells exposed to p38 MAPK inhibitor SB203580 served as TPX2 siRNA+SB203580 group. The expression of TPX2 at mRNA and protein levels was determined by RT-qPCR and Western blot. The cell viability was measured by MTT assay, the apoptosis was analyzed by flow cytometry. The protein levels of p38 MAPK, p-p38 MAPK, cleaved caspase-3 and Bcl-2 in the HR-8348 cells were determined by Western blot.RESULTS: After transfection, the expression of TPX2 at mRNA and protein levels was decreased in TPX2 siRNA-transfected cells (P<0.05). Transfection with siRNA-NC had no effect on TPX2 mRNA and protein levels in the cells. After knockdown of TPX2 expression, the viability of rectal cancer HR-8348 cells and the expression of Bcl-2 were decreased, while the apoptotic rate and the protein levels of cleaved caspase-3 and p-p38 MAPK/p38 MAPK were increased significantly reduced (P<0.05). Compared with TPX2 siRNA group, the apopto-tic rate and the protein levels of cleaved caspase-3 and p-p38 MAPK/p38 MAPK in TPX2 siRNA+SB203580 group were significantly decreased, while the viability was significantly increased (P<0.05).CONCLUSION: Knockdown of TPX2 expression promotes apoptosis of rectal cancer HR-8348 cells by activating p38 MAPK signaling pathway. 相似文献
2.
AIM:To investigate the effect of erianin on the viability and apoptosis of human lung cancer A549 cells and its possible mechanism. METHODS:A549 cells and BEAS-2B cells were cultured in vitro and treated with erianin at 10, 20, 40, 80 and 160 nmol/L for 48 h. The cell viability was measured by CCK-8 assay. The apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. The activity of superoxide dismutase (SOD) was detected by WST-8 method, and the content of malondialdehyde (MDA) was detected by barbituric acid method. The protein levels of nuclear factor E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), p38 MAPK, p-p38 MAPK, caspase-3 and cleaved caspase-3 were determined by Western blot.RESULTS:Erianin remarkably reduced the viability of A549 cells in a dose-dependent manner (P<0.05) with IC50 at 52.64 nmol/L. Erianin also induced apoptosis (P<0.05), increased ROS level and MDA content (P<0.05), diminished SOD activity (P<0.05), and down-regulated the protein levels of Nrf2, NQO1 and HO-1 (P<0.05), in a dose-dependent manner. Meanwhile, erianin up-regulated the levels of p-p38 MAPK and cleaved caspase-3 (P<0.05), and these effects were inhibited by N-acetyl-L-cysteine and SB203580 (P<0.05).CONCLUSION:Erianin may induce apoptosis of human lung cancer A549 cells most likely via inhibiting SOD activity and down-regulating the protein levels of Nrf2, NQO1 and HO-1, thus resulting in an increase in ROS and activation of p38 MAPK. 相似文献
3.
AIM: To investigate the effect of p38 MAPK signal pathway on cerulein-treated pancreatic acinar AR42J cells.METHODS: AR42J cells were divided into control group, cerulein group (treated with 10-8 mol/L of cerulein), and SB203580 group (treated with 10 μmol/L of SB203580 and 10-8mol/L of cerulein).The cells were harvested 3 h after treatment.Secretion rate of amylase was measured.The translocation of p-p38 MAPK to nuclei was imaged by immunofluorescence.The protein expression levels of p-p38 MAPK and TNF-α were detected by Western blotting.The activation of NF-κB was measured by electrophoretic mobility assay.RESULTS: Compared with control group, cerulein resulted in increases in the secretion rate of amylase and protein level of TNF-α (P<0.01), as well as the expression levels of p-p38 MAPK and NF-κB (P<0.01).Cerulein induced nuclear translocation of p-p38 MAPK.Compared with cerulein group, the secretion rate of amylase and protein level of TNF-α in SB203580 group decreased significantly (P<0.01).The expression of p-p38 MAPK and NF-κB also decreased greatly (P<0.05).Nuclear translocation of p-p38 MAPK was inhibited by SB203580.CONCLUSION: The p38 MAPK pathway involves in cerulein-induced pancreatic inflammatory response via regulating NF-κB. 相似文献
4.
YIN Xin-bao LIN Tian-xin XU Ke-wei HUANG Hai JIANG Chun HAN Jin-li HUANG Jian 《园艺学报》2009,25(7):1266-1270
AIM: To study the effect of 13-methyltetradecanoic acid (13-MTD) on bladder cancer T24 cell apoptosis and the underlying mechanisms. METHODS: T24 cells were treated with 13-MTD at different concentrations. MTT cell proliferation assay was used to observe the inhibitory effect. The cell cycle and cell apoptosis were displayed by FCM. Apoptosis index was investigated by TUNEL assay. Western blotting was used to detect the expression of apoptosis related proteins. RESULTS: p38 and JNK phosphorylation were presented 2 h after stimulated by 13-MTD, but AKT phosphorylation were inhibited. Cytochrome C was released from the intermembrane space of mitochondria 8 h later. No change of FADD and p-FADD was observed. Several downstream caspase substrates (PARP, lamin B, RB) were cleaved in 12 h. CONCLUSION: In the course of T24 cell apoptosis induced by 13-MTD, JNK/SAPK and p38MAPK signaling pathway are activated and the PI3K/AKT signaling pathway is inhibited. The substrates of caspase: PARP, Rb, lamin B are cleavaged by activated caspase enzymes to promote T24 cell apoptosis. 相似文献
5.
AIM：To investigate the role of thioredoxin nitration in the apoptosis of neonatal rat cardiomyocytes (NRCMs) induced by doxorubicin (DOX). METHODS：Cardiomyocytes treated with DOX were isolated from newborn Sprague-Dawley rats and cultured in vitro. NRCMs were treated with DOX alone (DOX group), pretreated with Mn (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), a peroxynitrite (ONOO-) scavenger, and then treated with DOX (MnTMPyP+DOX group), or treated with MnTMPyP alone (MnTMPyP group). NRCMs without any treatment served as a normal control (control group). The viability of the cells was examined by MTT assay, and the apoptosis was measured by Hoechst 33258 nuclear staining kit. The activity of caspase-3 was detected by spectrophotometry. The expression of cleaved poly(ADP-ribose) polymerase 1 (PARP-1), apoptosis signal-regulating kinase 1 (ASK1), phosphorylated ASK1 (p-ASK1), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) was measured by Western blotting. Immunoprecipitation and immunoblotting were performed to detect the formation of Trx-ASK1 and Trx-nitrotyrosine. RESULTS：DOX induced significant apoptosis of NRCMs. MnTMPyP could significantly attenuate the apoptosis induced by DOX. Compared with control group, Trx nitration in DOX group increased obviously. The increases in activity of caspase-3 and expression of cleaved PARP-1 and p-p38 MAPK were also observed, besides the expression of Trx-ASK1 compound and p-ASK1 decreased significantly (P<005). MnTMPyP could decrease the nitration of Trx. The decreases in activity of caspase-3 and expression of cleaved PARP-1 and p-p38 MAPK were detected in MnTMPyP+DOX group, while the expression of Trx-ASK1 compound and p-ASK1 increased significantly (P<005). CONCLUSION: DOX could induce significant apoptosis of NRCMs and increase Trx nitration. The process was significantly attenuated by pretreatment with MnTMPyP. Therefore, Trx nitration may play an important role in doxorubicin-induced apoptosis of cardiomyocytes. 相似文献
6.
AIM: To investigate the apoptotic effect of cepharanthine (CEP) on neonatal rat cardiomyocytes(NRCMs) and the underlying mechanisms. METHODS: MTT assay was used to detect the viability of the cells. CEP-induced apoptosis in NRCMs was evaluated by Hoechst 33342 staining and the expression of activated caspase-3. The phosphorylation levels of mitogen-activated protein kinases (MAPKs),such as extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAPK,were examined by Western blotting. The specific inhibitors of ERK and p38 MAPK were applied for identifying the roles of the corresponding signal pathways in CEP-induced apoptosis of cardiomyocytes. RESULTS: CEP inhibited the viability of NRCMs in a dose-and time-dependent manners. Positive nuclear fragmentation and activated caspase-3 were found in CEP-treated NRCMs. The phosphorylation levels of ERK and p38 MAPK were significantly elevated in CEP-treated NRCMs, but the change of JNK was not obvious. SB203580, an inhibitor of p38 MAPK, significantly alleviated the apoptotic effect induced by CEP. However, PD98059, an inhibitor of ERK1/2, did not significantly reduce the apoptotic effect.CONCLUSION: p38 MAPK is involved in CEP-induced apoptosis in NRCMs. 相似文献
7.
AIM: To investigate the anticancer effect of manumycin on abdominal metastatic breast cancer cell line - SK-BR-3 and its relationship with p38 MAPK. METHODS: The test of anticancer effect was performed by the method of MTT, apoptosis induced by manumycin and affected by SB203580, a specific p38 MAPK inhibitor, were examined by caspase-3 activity assay kit, and the protein expression was detected by immunoblotting assay. RESULTS: The inhibition rates at 24 h after treatment with manumycin of 6 μmol/L, 18 μmol/L, 54 μmol/L were (7.4±3.9)%, (21.0±4.4)% and (64.7±4.1)%, respectively and showed dosage-effect relationship. Compared with the control group, the survival rates of the last two treatment groups were decreased significantly (P<0.01). The value of IC50 24 h after treatment with manumycin was 42.5 μmol/L. Manumycin simultaneously activated caspase-3 protein, which was partly blocked by p38 MAPK inhibitor, SB203580. The results of immunoblotting showed that manumycin increased p38 MAPK protein phosphorylation. CONCLUSION: Manumycin exerts anticancer effect on SK-BR-3 cell line via inducing cell apoptosis, which is partly regulated by p38 MAPK. 相似文献
8.
AIM: To investigate the function of caspase-3 and mitogen-activated protein kinases (MAPKs) in allogeneic CD8+T cell-induced apoptosis of vascular endothelial cells. METHODS: Allogeneic CD8+T cells were isolated from PBMC by positive selection using magnetic beads coated with anti-CD8 antibody. After cocultured with allogeneic CD8+T cells, apoptosis of human umbilical vein endothelial cells (HUVECs) and human dermal microvascular endothelial cells (HDMECs) were detected by AnnexinV-FITC labeling. Western blotting was used to examine the change of MAPK and caspase-3 expression in the vascular endothelial cells. The influence of SB203580 (inhibitor of p38MAPK), SP600125 (inhibitor of JNK), PD98059 (inhibitor of ERK), Z-DEVD-FMK (a caspase-3-specific peptide inhibitor) on apoptosis was also examined. RESULTS: At 24 h and 48 h time-point, the apoptosis rates of HUVECs were 41.7%±10.1% and 29.4%±8.3%, respectively (P<0.01, vs untreated HUVECs); the apoptosis rates of HDMECs were 28.9%±7.2% and 15.2%±4.8%, respectively (P<0.01, vs untreated HDMECs). These effects were largely prevented by Z-DEVD-FMK and SB203580 (P<0.05). Allogeneic CD8+T cells enhanced cleavage of caspase-3 and led to p38MAPK phospholation. CONCLUSION: Caspase-3 and p38MAPK mediate allogeneic CD8+T cells-induced apoptosis of vascular endothelial cells. 相似文献
9.
AIM:To evaluate the roles of p66Shc-mitochondrial signal pathway in apoptosis of human renal tubular epithelial cells induced by cisplatin. METHODS:The human renal tubular epithelial cells were cultured in vitro. The levels of p66Shc and phospho-p66Shc(Ser36) protein were detected by Western blotting. The cells were divided into control group, cisplatin group and cisplatin+p66ShcS36A(p66Shc with Ser mutating into Ala at position 36) group. The effects of p66Shc on cisplatin-induced cellular reactive oxygen species (ROS), mitochondrial ROS and apoptosis were measured by confocal microscopy. The expression of the proteins related to apoptosis mitochondrial signal transduction pathway was analyzed by Western blotting. RESULTS:Cisplatin induced p66Shc phosphorylation, but did not affect the expression of p66Shc. Cisplatin enhanced apoptosis and production of both cellular and mitochondrial ROS, release of cytochrome C and expression of caspase-9, which were inhibited by the transfection of p66ShcS36A. CONCLUSION: Cisplatin induces apoptosis of human renaltubular epithelial cells through p66Shc-mitochondrial signal pathway. 相似文献
10.
AIM: To study the effect of cellular repressor of E1A-stimulated genes(CREG) and its mechanism on apoptosis of human umbilical vein endothelial cells (HUVECs) induced by etoposide (VP-16).METHODS: Primary HUVECs were cultured. RetroviraI eukaryotic expression vectors pLNCX-CREG and pLXSN-shRNA-CREG were transfected into HUVECs. The stable cell clone was selected and obtained by screening with G418 (800 mg/L) and the puromycin (2.5 mg/L), respectively. CREG expression was detected by Western blotting. The cells with overexpression of CREG (H-C) and those with CREG down-regulation (H-S) were pretreated with apoptotic inducer VP-16 at 100 μmol/L for 6 h. The apoptotic rates of the 3 kinds of cells were analyzed by TUNEL and flow cytometry with annexin V/PI dualstaining. Furthermore, the protein levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in the 3 kinds of cells were analyzed by Western blotting. The p38-specific inhibitor SB203580(20 μmol/L)was used to investigate the effects of p-p38 expression on apoptosis. RESULTS: Western blotting showed that CREG expression was obviously increased up to 160% in H-C compared to HUVECs. However, CREG expression in H-S cells was identified to be down-regulated to 70% compared with HUVECs. TUNEL assay and annexin V/PI dual-color FACS showed that the apoptotic rate was dramatically increased in H-S cells,but decreased in H-C cells. Subsequently, Western blotting exhibited that p-p38 expression was increased in H-S cells compared to HUVECs and H-C cells. When the H-S was pretreated with SB203580, the apoptotic rate was decreased. CONCLUSION: CREG overexpression might prevent HUVECs from apoptosis by inhibiting p38 MAPK activition. 相似文献
11.
AIM: In this study, we investigated the anticancer effect and mechanisms of manumycin on pancreatic cancer cell line-Panc-1 and the role of p38MAPK pathway in apoptosis. METHODS: The test of anticancer effect was performed by MTT assay. Apoptosis was induced in the cells by manumycin and then treated with SB203580, a specific p38MAPK inhibitor. A quantitative caspase-3 activity assay kit was used in this experiment. RESULTS: Manumycin (6 μmol/L, 18 μmol/L, 54 μmol/L) significantly inhibited cell growth of pancreatic cancer cell line Panc-1. The inhibition rates 24 h after treatment with 6 μmol/L, 18 μmol/L and 54 μmol/L manumycin were 8.9%, 21.9% and 67.0%, respectively. Compared with the control group, the survival levels of the last two groups were of significant statistical difference (P<0.01). The anticancer effects also showed dosage-effect relationship, the value of IC50 24 h after treatment was 34.7 μmol/L. In addition, this reagent simultaneously activated caspase-3 protein, which was partly blocked by p38MAPK specific inhibitor, SB203580. CONCLUSION: Manumycin exerted anticancer effect on Panc-1 cell line via inducing cell apoptosis, which was partly regulated by p38MAPK. 相似文献
12.
AIM:To investigate the effect of P21 on cisplatin-induced renal tubular epithelial cells injury.METHODS:The expression of P21 at mRNA and protein levels in cisplatin treated human renal tubular epithelial cells (HK-2) cells was determined by RT-qPCR and Western blot. Over-expression of P21in the HK-2 cells was induced by the transfection of pcDNA3-P21. The cell viability and cell apoptosis were detected by CCK-8 assay and flow cytometry, respectively. Furthermore, the protein expression of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), caspase-3, glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), and phosphorylation level of eucaryotic translation initiation factor 2α (eIF2α) and protein kinase R-like endoplasmic reticulum kinase (PERK) were detected by Western blot.RESULTS:Cisplatin increased the mRNA and protein levels of P21 in a time-and concentration-dependent manner in the HK-2 cells. Over-expression of P21 inhibited cisplatin-induced cell apoptosis, and down-regulated the expression of KIM-1 and NGAL. Furthermore, Over-expression of P21 decreased the protein levels of GRP78, p-PERK, p-eIF2α, CHOP and cleaved caspase-3.CONCLUSION:Over-expression of P21 attenuates cisplatin-induced HK-2 cells injury, and the mechanism may be related to the modulation of endoplasmic reticulum stress pathway and inhibition of cell apoptosis. 相似文献
13.
AIM: To explore the effects of p38 mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinases (PI3K)/Akt on interleukin (IL)-6, the endothelin (ET)-1-mediated process of airway fibroblast activation induced by injured human bronchial epithelial cells (HBE). METHODS: Human primary cultured airway fibroblasts were co-cultured with HBE pre-treated with or without poly-L-arginine (PLA). The procedure was also performed in the presence or absence of p38 MAPK selective inhibitor SB203580, PI3K selective inhibitor LY294002 or ETA receptor blocker BQ123, respectively. Immunostaining, Western blotting or ELISA were used for detecting α-smooth muscle actin (α-SMA) expression, the activities of p38 MAPK and Akt in fibroblasts or IL-6 levels in supernatants of fibroblasts. In addition, fibroblasts were mixed with soluble collagen and cultured with HBE treated as the same mentioned above, the gel contraction was measured by serial area measurements. RESULTS: ET-1 and IL-6 levels ［(13.69±1.36) ng/L, (56.7±10.7) ng/L］ in the supernatants of fibroblasts cultured with injured HBE were significantly higher than those in the supernatants of fibroblasts cultured with HBE ［(3.79±0.64) ng/L, (15.5±3.2) ng/L］. BQ123, SB203580 or LY294002 decreased IL-6 levels ［(27.2±3.1) ng/L, (31.5±3.6) ng/L, (41.3±3.2) ng/L］ differently in the supernatants of fibroblasts induced by injured HBE. Activation of p38 MAPK preceded Akt in fibroblasts cultured with injured HBE. BQ123 reduced the phosphorylation levels of p38 MAPK and Akt. SB203580 concentration-dependently attenuated Akt phosphorylation, while LY294002 had little effect on p38 MAPK phosphorylation. Fibroblasts expressed more α-SMA after cultured with injured HBE and showed significant increase in the gel contraction compared to fibroblasts cultured with HBE ［percentage of gel contraction: (61.2±2.7)% vs (15.4±7.3)%］, all these effects were diminished or inhibited by BQ123, SB203580 or LY294002. Furthermore, the effects of BQ123 and SB203580 on decreased gel contraction were stronger than the effect of LY294002. CONCLUSION: ET-1 exerts a key role in the airway fibroblasts activation induced by injured HBE through activating p38 MAPK, PI3K/Akt signaling and promoting IL-6 expression. 相似文献
14.
AIM: To investigate the expression of p38 mitogen-activated protein kinase (p38MAPK) in the kidney after unilateral ureteral obstruction (UUO) in rats and the functional role of it on apoptosis and fibrosis.METHODS: Eighteen Wistar rats underwent UUO were killed at 3, 7, 14 days. Additional 7 rats were sham operated. Histological changes were observed by HE and Masson staining. Immunohistochemistry study was performed on renal tissue for proliferating cell nuclear antigen (PCNA). Apoptotic cells were determined by terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) and the electrophoresis analysis of genomic DNA. Western blotting of cysteinyl aspartate specific proteinase-3 (caspase-3), p38MAPK and p-p38MAPK were measured.RESULTS: UUO induced a significant increase in renal tubular and interstitial cell apoptosis, immunohistochemistry of PCNA and Western blotting of caspase-3, p-p38MAPK as well as severe morphology changes. However, there was no significant difference between UUO and the control in Western blotting of p38MAPK.CONCLUSION: An in vivo model of renal fibrosis after UUO demonstrates that activated or phosphorylated p38MAPK plays a role in apoptosis of renal tubulointerstitial cells. 相似文献
15.
AIM: To observe the role of p38 mitogen-activated protein kinase (p38 MAPK)-heat-shock protein 27 (HSP27) signaling pathway in lipopolysaccharide-induced acute lung injury (ALI) in rats. METHODS: Wistar rats were randomly divided into control group, ALI group and ALI+SB203580 group. After the experimental model was established, the rats were sacrificed. The pathological changes of the lung and the changes of F-actin and G-actin in the endothelial cells were observed. The ratio of wet weight to dry weight (W/D) of the lung tissues was measured. The protein levels in bronchoalveolar lavage fluid (BALF) were detected. The levels of IL-6 and TNF-α in serum and BALF were tested. The concentrations of p-p38 and p-HSP27 in the lung were determined. RESULTS: In ALI group, the protein levels in BALF and W/D ratio of the lung increased significantly at 2 h. The levels of TNF-α and IL-6 in serum and BALF began to increase at 2 h, which had significant difference as compared with control group. Aleolar epithelial swelling, alveolar walls widening, alveolar interstitial and cavity edema, and the exudation of alveolar inflammation cells, red blood cells and protein were observed in ALI group. The protein levels in BALF and W/D ratio of the lung in ALI+SB203580 group were much less than those in ALI group. The exudation of alveolar inflammation cells, red blood cells and protein, and the interstitial and alveolar edema in ALI+SB203580 group alleviated as compared with ALI group. The expression of p-p38 MAPK and p-HSP27 in the lung at 2 h in ALI group was higher than that in control group. F-actin expression in ALI group obviously increased than that in control group at time points of 0 h and 8 h. Compared with ALI group, the expression of p-HSP27 and F-actin in ALI+SB203580 group was reduced. CONCLUSION: Lipopolysaccharide activates p38 MAPK-HSP27 signaling pathway and induces lung injury. Blockage of p38 MAPK-HSP27 signaling pathway may reduce lung injury. 相似文献
16.
LAI Li-na SONG Li-hua ZHANG Xiao-jing ZHANG Xiao-yi LEI Jing-wen LIU Fang GUO Chun-hua SONG Xiao-liang 《园艺学报》2014,30(12):2201-2205
AIM: To investigate the effect of polysaccharide from Fructus corni(PFC) on cardiomyocytes against hypoxia/reoxygenation (H/R) injury and its possible relationship with ROS/PKC/p38 MAPK pathway.METHODS: Primary cardiomyocytes were isolated from neonatal SD rats and randomly divided into normal group, H/R group, PFC (20 mg/L, 100 mg/L and 200 mg/L) preconditioning+H/R groups, chelerythrine+PFC (100 mg/L)+H/R group and SB203580+PFC (100 mg/L)+H/R group. The cell viability was measured by inverted microscopic observation. Apoptosis in the cardiomyocytes was detected by Hoechst 33258 staining and fluorescence microscopy. The levels of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the cell culture supernatants, and the reactive oxygen species (ROS) in the cells were also measured by microplate reader. The protein levels of PKC, p-p38 MAPK and HSP70 in the cells were detected by Western blotting.RESULTS: Compared with normal group, the cell viability and beating frequency were decreased in H/R group. LDH and ROS contents, apoptotic rate and p-p38 MAPK level increased significantly (P<0.01). Compared with H/R group, PFC preconditioning increased beating frequency, SOD activity and the protein level of PKC and HSP70, and decreased ROS production, the protein level of p-p38 MAPK and cell apoptotic rate. However, the effect of PFC was inhibited by chelerythrine or SB203580.CONCLUSION: PFC may protect cardiomyocytes from hypoxia/reoxygenation injury. Its mechanism is possibly involved in the inhibition of ROS via increasing the activity of SOD and the activation of PKC, and suppression of excessive activation of p38 MAPK. 相似文献
17.
AIM: To investigate the role of p38 MAPK signaling pathway in the receptor-mediated endocytosis. METHODS: The effects of p38 MAPK on the receptor-mediated endocytosis were observed by using Alexa 594-conjugated Transferrin, in the presence of p38 specific inhibitor SB203580 or ERK pathway specific inhibitor PD98059, or using p38 knockout techniques. RESULTS: In the process of receptor-mediated endocytosis, p38 was activated by phosphorylation. Furthermore, the receptor-mediated endocytosis was inhibited by pretreatment with SB203580 or p38 knockout, while pretreatment with PD98059 had no effect on this process.CONCLUSION: p38 MAPK signaling pathway plays a role in the regulation of receptor-mediated endocytosis. 相似文献
18.
AIM: To study the role of p38 mitogen-activated protein kinase (p38MAPK) activation in high glucose-induced collagen Ⅲ synthesis in NRK52E cells. METHODS: Normal rat tubular epithelial cell line NRK52E was cultured in D-glucose of different concentrations, pretreated with SB203580 and collected at different time points. The levels of phospho-p38MAPK and extracellular matrix collagen Ⅲ were examined by Western blotting. RESULTS: The activation of p38MAPK was shown to be dependent upon D-glucose concentration and the time-course. Pretreatment with SB203580 blocked p38MAPK activation induced by high concentration of D-glucose in NRK52E cells. CONCLUSIONS: The activation of p38MAPK induced by high concentration of glucose may play a role in diabetic interstital renal fibrosis. SB203580 has a potential value of clinical applications in the prevention and treatment of diabetic nephropathy. 相似文献
19.
AIM: To investigate the role of p38 MAPK/ATF-2 pathway in C-relative protein (CRP)-induced endothelial cell activation. METHODS: Human coronary artery endothelial cells (HCAEC) were cultured and were used between passages 3 and 7. CRP served as a stimulus for endothelial cell activation. Western blotting was performed to determine the expression and phosphorylation of eNOS, p38 and ATF2. ELISA was carried out to detect the levels of ICAM-1, VCAM-1 and MCP-1 released from HCAEC. Pharmacological p38 inhibitors SB203580 and SB202190 were used to determine the effect of p38/ATF-2 pathway. RESULTS: CRP reduced the p-eNOS level in a concentration-dependent manner and induced the release of ICAM-1, VCAM-1 and MCP-1. The p38/ATF-2 pathway was activated by CRP treatment. SB203580 and SB202190 partially rescued p-eNOS level and suppressed the secretion of ICAM-1, VCAM-1 and MCP-1. CONCLUSION: p38MAPK/ATF-2 pathway participates in CRP-induced endothelial activation. 相似文献
20.
AIM：To investigate the effect of dexmedetomidine (Dex) on neuronal apoptosis induced by isoflurane (Iso) and its relationship with the expression of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) proteins in the hippocampus of neonatal rats. METHODS：Forty-eight neonatal SD rats at postnatal day 7 were randomly divided into control group (Con), Dex group, Iso group and Iso combined with Dex (Iso+Dex) group. Rats in Iso and Iso+Dex groups were exposed to 0.75% Iso for 6 h, while rats in Con and Dex groups were exposed to air for 6 h. Rats were intraperitoneally injected with 25 μg·kg-1 Dex (Dex and Iso+Dex groups) or 150 μL saline (Con and Iso groups) 20 min before exposure and 2 and 4 h after exposure. After the termination of anesthesia, the neuronal apoptosis in hippocampal CA1 region was detected by TUNEL staining, and the protein expression of cleaved caspase-3, phospho-p38 (p-p38), p38, phospho-JNK (p-JNK) and JNK in hippocampal tissues was detected by Western blotting. RESULTS：The number of TUNEL positive cells in hippocampal CA1 region of the rats in Iso group was increased by 447.57% (P<0.01) compared with Con group, while Dex significantly inhibited the increased TUNEL positive cells in Iso group by 75.18% (P<0.01). The expression of cleaved caspase-3 protein in Iso group was increased by 126.29% (P<0.01) compared with Con group, while Dex reversed the increased cleaved caspase-3 protein expression (P<0.01). Iso significantly increased the phosphorylation of p38 and JNK proteins (P<0.01), while Dex reversed the increased p-p38 and p-JNK proteins (P<0.01). CONCLUSION：Dex attenuates Iso-induced neuroapoptosis in the hippocampus of neonatal rats through inhibiting the phosphorylation of p38 and JNK proteins. 相似文献