Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we investigated the effect of bryostatin-1 (Bryo-1), an antineoplastic agent, on dendritic cell (DC) maturation, activation, and functions. Murine bone marrow-derived DCs on culture with Bryo-1 alone, Bryo-1 + calcium ionophore (CI), but not CI alone exhibited morphologic changes characteristic of mature DCs and expressed increased levels of CD40, CD80, and CD86. Moreover, Bryo-1 + CI-treated DCs exhibited enhanced antigen-presenting ability to naive and antigen-specific T cells and alloreactive T cells. Bryo-1 + CI-mediated activation of DCs involved protein kinase C (PKC), especially PKC-alpha, -delta, and -iota, and addition of PKC inhibitors impaired their ability to activate T cells. Bryo-1 + CI treatment of DCs did not activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, p38 MAPK, or stress-activated protein kinase/c-Jun NH2-terminal kinase pathways. Finally, treatment of DCs with Bryo-1 alone and Bryo-1 + CI, but not CI alone, induced nuclear translocation of nuclear factor kappaB as studied by confocal microscopy. DCs generated from human peripheral blood monocytes or from human cord blood CD34+ hematopoietic stem cells, when cultured with Bryo-1 + CI, also showed maturation and increased T-cell stimulatory activity. Bryo-1 + CI was more potent in inducing maturation and activation of DCs when compared with other agents such as tumor necrosis factor alpha, lipopolysaccharide, or phorbol 12-myristate 13-acetate + CI. Collectively, the current study shows for the first time that Bryo-1 alone or in combination with CI may promote the maturation of DCs and therefore may be useful in development of DC-based cancer immunotherapy.
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PMID:Bryostatin-1 enhances the maturation and antigen-presenting ability of murine and human dendritic cells. 1537 94

In the present study, we investigated the role of protein kinase C (PKC) isoforms during hypoxia in heart-derived H9c2 cells. Hypoxia caused a rapid translocation of PKC-delta from soluble to particulate fraction and a downregulation of PKC-epsilon and PKC-zeta, whereas PKC-alpha and PKC-beta I remained unaltered. When H9c2 cells were pretreated with PKC-delta inhibitor rottlerin (3 microM), hypoxia-induced apoptotic and necrotic cell death were significantly increased. Hypoxic insult also caused an activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK with no change in c-Jun NH(2)-terminal protein kinase (JNK) phosphorylation. Hypoxia-induced cell death was increased by treatment with ERK1/2 inhibitor U0126 (10 microM), but attenuated by p38 MAPK inhibitor SB202190 (10 microM). Treatment with rottlerin completely blocked the hypoxia-induced ERK phosphorylation, whereas it significantly increased p38 MAPK phosphorylation. The hypoxia-induced translocation of PKC-delta was not altered by U0126 and/or SB202190. From these results, it is suggested that hypoxia causes a rapid translocation of PKC-delta and subsequently ERK activation and p38 inactivation, rendering H9c2 cells resistant to hypoxia-induced cell death.
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PMID:Role of PKC-delta during hypoxia in heart-derived H9c2 cells. 1563 96

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) enhances reepithelialization in wounds. Estrogen is known to promote cutaneous wound repair. We examined the in vitro effects of 17beta-estradiol (E2) on HB-EGF production by human keratinocytes. E2 or membrane-impermeable BSA-conjugated E2 (E2-BSA) increased HB-EGF secretion, mRNA level, and promoter activity in keratinocytes. E2 or E2-BSA enhanced in vitro wound closure in keratinocytes, and the closure was suppressed by anti-HB-EGF antibody. Activator protein-1 (AP-1) and specificity protein 1 (Sp1) sites on HB-EGF promoter were responsible for the E2- or E2-BSA-induced transactivation. Antisense oligonucleotides against c-Fos, c-Jun, and Sp1 blocked E2- or E2-BSA-induced HB-EGF transactivation. E2 or E2-BSA enhanced DNA binding and transcriptional activity of AP-1 and generated c-Fos/c-Jun heterodimers by inducing c-Fos expression. E2 or E2-BSA enhanced DNA binding and transcriptional activity of Sp1 in parallel with the enhancement of Sp1 phosphorylation. These effects of E2 or E2-BSA were not blocked by the nuclear estrogen receptor antagonist ICI-182,780 or anti-estrogen receptor-alpha or -beta antibodies but were blocked by inhibitors of G protein, phosphatidylinositol-specific PLC, PKC-alpha, and MEK1. These results suggest that E2 or E2-BSA may enhance HB-EGF production via activation of AP-1 and Sp1. These effects of E2 or E2-BSA may be dependent on membrane G protein-coupled receptors different from nuclear estrogen receptors and on the receptor-mediated activities of phosphatidylinositol-specific PLC, PKC-alpha, and MEK1. E2 may enhance wound reepithelialization by promoting HB-EGF production in keratinocytes.
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PMID:17beta-estradiol enhances heparin-binding epidermal growth factor-like growth factor production in human keratinocytes. 1576 Dec 12

Skeletal muscle undergoes a significant reduction in tension upon unloading. To explore intracellular signalling mechanisms underlying this phenomenon, we investigated twitch tension, the ratio of actin/myosin filaments, and activities of key signalling molecules in rat soleus muscle during a 3-week hindlimb suspension and 2-week reloading. Twitch tension and myofilament ratio (actin/myosin) gradually decreased during unloading but progressively recovered to initial levels during reloading. To study the involvement of stress-responsive signalling proteins during these changes, the activities of protein kinase C alpha (PKCalpha) and three mitogen-activated protein kinases (MAPKs)--c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38 MAPK--were examined using immunoblotting and immune complex kinase assays. PKCalpha phosphorylation correlated positively with the tension (Pearson's r = 0.97, P < 0.001) and the myofilament ratio (r = 0.83, P < 0.01) over the entire unloading and reloading period. Treatment of the soleus muscle with a PKC activator resulted in a similar paralleled increment in both PKCalpha phosphorylation and the alpha-sarcomeric actin expression. The three MAPKs differed in the pattern of activation in that JNK activity peaked only for the first hours of reloading, whereas ERK and p38 MAPK activities remained elevated during reloading. These results suggest that PKCalpha may play a pivotal role in converting loading stress to intracellular changes in contractile proteins that determine muscle tension. Differential activation of MAPKs may also help alleviate muscle damage, modulate energy transport and/or regulate the expression of contractile proteins upon altered loading.
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PMID:Differential activation of stress-responsive signalling proteins associated with altered loading in a rat skeletal muscle. 1614 53

c-Jun NH(2)-terminal kinase (JNK), a member of the MAPK family of protein kinases, is a stress-response kinase that is activated by proinflammatory cytokines and growth factors coupled to membrane receptors or through nonreceptor pathways by stimuli such as heat shock, UV irradiation, protein synthesis inhibitors, and conditions that elevate the levels of reactive oxygen intermediates (ROI). Ischemia followed by reperfusion or hypoxia with reoxygenation represents a condition of high oxidative stress where JNK activation is associated with elevated ROI. We recently demonstrated that the activation of JNK by this condition is initiated by ROI generated by mitochondrial electron transport and involves sequential activation of the proline-rich kinase 2 and the small GTP-binding factors Rac-1 and Cdc42. Here we present evidence that protein kinase C (PKC) and transforming growth factor-beta-activated kinase-1 (TAK-1) are also components of this pathway. Inhibition of PKC with the broad-range inhibitor calphostin C, the PKC-alpha/beta-selective inhibitor Go9367, or adenovirus-expressing dominant-negative PKC-alpha blocked the phosphorylation of proline-rich kinase 2 and JNK. Reoxygenation activated the mitogen-activated protein kinase kinase kinase, TAK-1, and promoted the formation of a complex containing Rac-1, TAK-1, and JNK but not apoptosis-stimulating kinase-1 or p21-activated kinase-1, which was detected within the first 10 min of reoxygenation. These results identify two new components, PKC and TAK-1, that have not been previously described in this signaling pathway.
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PMID:PKC-alpha and TAK-1 are intermediates in the activation of c-Jun NH2-terminal kinase by hypoxia-reoxygenation. 1720 6

The purpose of this study was to investigate the inhibitory effect of 24-kDa glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein) on glucose/glucose oxidase (G/GO)- or hypoxanthine/xanthine oxidase (HX/XO)-induced cell proliferation in Chang liver cells. We found that ZPDC glycoprotein has significant scavenging effect on the production of intracellular H2O2 without cytotoxicity in G/GO- or HX/XO-treated in Chang liver cells. In the G/GO or HX/XO-stimulated protein kinases activity, ZPDC glycoprotein inhibited translocation of protein kinase C alpha (PKCalpha) to membrane and phosphorylation of extracellular signal-regulated kinase, p38 MAP kinase and c-Jun N-terminal kinase, respectively. In the G/GO or HX/XO-stimulated transcriptional activity, ZPDC glycoprotein also blocked the DNA binding activities of nuclear factor-kappa B and activator protein-1 and attenuated the activities of p50, p65, c-Jun and c-Fos, respectively. Finally, in the G/GO or HX/XO-stimulated cell proliferation, the activity of proliferating cell nuclear antigen was significantly blocked by treatment with ZPDC glycoprotein as well as protein kinase C inhibitor and mitogen-activated protein kinase inhibitors. On the basis of these results, we speculate that this glycoprotein is one of the natural antioxidants and of the modulators on abnormal activation of cell proliferation-related molecules in Chang liver cells.
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PMID:Phytoglycoprotein (24 kDa) inhibits expression of PCNA via PKCalpha and MAPKs in oxygen radical-stimulated Chang liver cells. 1850 55

Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury. However, how Claudin-15 affects Schwann cell function is still unknown. This study aimed to identify the effects of Claudin-15 on proliferation and apoptosis of Schwann cells cultured in vitro and explore the underlying mechanisms. Primary Schwann cells were obtained from rats. Claudin-15 in Schwann cells was knocked down using siRNA (siRNA-1 group) compared with the negative control siRNA transfection group (negative control group). Claudin-15 in Schwann cells was overexpressed using pGV230-Claudin-15 plasmid (pGV230-Claudin-15 group). The pGV230 transfection group (pGV230 group) acted as the control of the pGV230-Claudin-15 group. Cell proliferation was analyzed with EdU assay. Cell apoptosis was analyzed with flow cytometric analysis. Cell migration was analyzed with Transwell inserts. The mRNA and protein expressions were analyzed with quantitative polymerase chain reaction assay and western blot assay. The results showed that compared with the negative control group, cell proliferation rate was up-regulated; p-AKT/AKT ratio, apoptotic rate, p-c-Jun/c-Jun ratio, mRNA expression of protein kinase C alpha, Bcl-2 and Bax were down-regulated; and mRNA expression of neurotrophins basic fibroblast growth factor and neurotrophin-3 were increased in the siRNA-1 group. No significant difference was found in cell migration between the negative control and siRNA-1 groups. Compared with the pGV230 group, the cell proliferation rate was down-regulated; apoptotic rate, p-c-Jun/c-Jun ratio and c-Fos protein expression increased; mRNA expression of protein kinase C alpha and Bax decreased; and mRNA expressions of neurotrophins basic fibroblast growth factor and neurotrophin-3 were up-regulated in the pGV230-Claudin-15 group. The above results demonstrated that overexpression of Claudin-15 inhibited Schwann cell proliferation and promoted Schwann cell apoptosis in vitro. Silencing of Claudin-15 had the reverse effect and provided neuroprotective effect. This study was approved by the Experimental Animal Ethics Committee of Jilin University of China (approval No. 2016-nsfc001) on March 5, 2016.
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PMID:Claudin-15 overexpression inhibits proliferation and promotes apoptosis of Schwann cells in vitro. 3153 66


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