Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of nine flavonoids isolated from Scutellariae radix on interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)-induced adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVECs). Among them, we found that baicalein (5,6,7-trihydroxy flavone) dose-dependently inhibited IL-1 beta and TNF-alpha-induced endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions. Its 50% inhibitory concentrations (IC50) for the IL-1 beta-induced ELAM-1 and ICAM-1 expressions were 2.3 x 10(-5) M and 4.0 x 10(-5) M, respectively. The IC50 for the TNF-alpha-induced ELAM-1 and ICAM-1 expressions were 1.5 x 10(-5) M and 3.1 x 10(-5) M, respectively. In addition, protein C-kinase (PKC) inhibitor H7 also inhibited the ELAM-1 and ICAM-1 expressions induced by IL-1 beta and TNF-alpha.
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PMID:Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta- and tumor necrosis factor alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. 923 65

Red blood cells (RBC) from patients with diabetes mellitus exhibit an increased propensity to adhere to cultured human umbilical vein endothelial cells (HUVEC) as a result of interaction of advanced glycation end products with their counter receptors, contributing to the pathogenesis of vascular complications. We determined whether the interaction of diabetic RBC with HUVEC induced cellular oxidant stress that would culminate in adherence and diapedesis of monocytes, these being initiating events in endothelial injury and atherogenesis. We show that the adherence of diabetic RBC (2% hematocrit), but not normal RBC, to HUVEC results in a fourfold increase in the production of lipid peroxides. Furthermore, diabetic RBC-induced oxidant stress causes a sixfold increase in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation and doubles transendothelial migration of monocyte-like HL-60 cells; both are blocked by antioxidants and protein kinase C (PKC) inhibitors. Our results show that the adherence of diabetic RBC to endothelial cells initiates a cascade of cellular events resulting in PKC activation, causing PECAM-1 phosphorylation and concomitant transendothelial migration of monocytes. The increased diapedesis of monocytes, brought about by the interaction of diabetic RBC across vascular endothelium, may play an important role in accelerated atherosclerosis and cardiovascular disease in diabetics.
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PMID:Diabetic RBC-induced oxidant stress leads to transendothelial migration of monocyte-like HL-60 cells. 927 91

Reactive oxygen species (ROS) are believed to cause vascular injury in the pathophysiology of atherosclerosis, diabetes, and vasoocclusion in sickle cell disease. Studies have shown that ROS causes increased adhesion of monocytes and neutrophils to the endothelium. We investigated the effects of tert-butylhydroperoxide (t-BuOOH), an inducer of oxidant stress, to determine the cellular signaling pathway leading to the transendothelial migration of polymorphonuclear leukocytes. Our studies revealed that signaling by t-BuOOH in human umbilical vein endothelial cells (HUVECs) causes a twofold increase in the transendothelial migration of monocyte-like HL-60 cells and a fivefold increase in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation. The transmigration induced by t-BuOOH was inhibited by an antibody to PECAM-1. These events were inhibited by antioxidants and inhibitors of protein kinase C, p21ras and glutathione synthesis. However, treatment of HUVECs with the phosphatase inhibitor calyculin A augmented the t-BuOOH-mediated transendothelial migration of monocytes and PECAM-1 phosphorylation. Our results suggest that oxidative stress can induce the transendothelial migration of monocytes as a result of phosphorylation of PECAM-1, a crucial event in the diapedesis of leukocytes during pathophysiology of vascular diseases.
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PMID:Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PECAM-1. 931 33

Nonantigen specific adhesion systems lymphocyte function-associated antigen 1/intercellular adhesion molecule (LFA-1/ICAM-1) and cluster designation 2/lymphocyte function-associated antigen 3 (CD2/LFA-3) are considered a crucial step in immune-mediated cell-cell adhesion reactions. In particular, the LFA-1/ICAM-1 system is deeply involved in major histocompatibility system (MHC)-restricted and non-MHC-restricted cellular cytotoxicity of effector cells against cancer tissues. We have investigated in human thyroid carcinoma cell lines the role of the protein kinase C (PKC) pathway on ICAM-1 expression. Incubation with tissue plasminogen activator (TPA), an agonist of PKC, of two papillary (NPA and TPC-1) and one anaplastic (ARO) carcinoma cell lines induced an ICAM-1 upregulation of both protein and mRNA production. This phenomenon was dependent on RNA and protein synthesis and was inhibited by PKC antagonists such as staurosporine and H-7. A parallel increase in the soluble form of ICAM-1 followed the upregulation of cellular ICAM-1 levels induced by TPA. In conclusion, the PKC pathway is involved in the regulation of ICAM-1 expression in human thyroid carcinoma cell lines. Further studies are necessary to clarify the effects of the PKC pathway on the diffusion of thyroid tumors.
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PMID:Intercellular adhesion molecule-1 is upregulated via the protein kinase C pathway in human thyroid carcinoma cell lines. 949 49

In Plasmodium falciparum malaria, large proportions of resident macrophages and circulating monocytes and leukocytes contain massive amounts of the malarial pigment, hemozoin. Previous studies have shown that important functions (e.g., the generation of the oxidative burst, the ability to repeat phagocytosis, and protein kinase C activity) were severely impaired in hemozoin-loaded monocytes. Expression of membrane antigens directly involved in the immune response and in the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded human monocytes was studied. Expression of major histocompatibility complex (MHC) class II after gamma interferon stimulation was blocked in hemozoin-loaded monocytes at the protein expression and gene transcription levels but was preserved in control monocytes loaded with opsonized latex beads or anti-D(Rho)-immunoglobulin G (IgG)-opsonized human erythrocytes. Expression of CD54 (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also decreased in hemozoin-loaded monocytes. Expression of MHC class I, CD16 (low-affinity Fc receptor for aggregated IgG), CD32 (low-affinity Fc receptor for aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for complement component iC3b [CR3]), CD35 (receptor for complement components C3b and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specifically affected by hemozoin loading. These results suggest that hemozoin loading may contribute to the impairment of the immune response and the derangement of antigen presentation reported in previous studies of P. falciparum malaria.
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PMID:Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes. 952 87

Antisense oligodesoxynucleotides (ODN) provide a novel strategy to inhibit RNA transcription and thereby the synthesis of the gene product. Because antisense ODN hybridize with the mRNA strand, they are highly specific. Their backbone structure has been modified to phosphorothioates or phosphoamidates so that they can better withstand degradation after delivery. We have shown that antisense ODN are a useful research tool to elucidate intracellular processes. The example we provide involves the inhibition of PKC signaling. Furthermore, we have shown the potential clinical utility of antisense treatment. We successfully inhibited the expression of the surface adhesion molecule ICAM-1 with antisense ODN in a model of reperfusion injury. This model is highly applicable to the problem of delayed graft function in humans. However, "getting there" is a major problem and clearly less than half the fun. Cationic substances such as lipofectin have worked sufficiently well in the experimental setting. Viral gene transfer offers a possibility; however, viruses produce an additional series of problems. Liposomes may not provide sufficient transfer efficiency. Coating liposomes with viral fusion proteins may offer an ideal way with which to deliver the goods into the cytoplasm of the target cell.
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PMID:Antisense oligodesoxynucleotide strategies in renal and cardiovascular disease. 960 85

A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.
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PMID:Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells. 964 16

DNAX accessory molecule-1 (DNAM-1) is a signal-transducing adhesion molecule involved in the cytolytic function mediated by CTL and NK cells. In the present study, we have investigated various perimeters of DNAM-1-mediated signaling and adhesion. Although adhesion of DNAM-1 to its ligand does not require divalent cations, protein synthesis, or RNA transcription, activation of protein kinase C (PKC) is required for DNAM-1 functioning. Furthermore, mutation of the putative PKC-binding site in the cytoplasmic domain of DNAM-1 (Ser329 to Phe329) prevents both ligand binding and PMA-induced phosphorylation of the DNAM-1 receptor. These results indicate that PKC phosphorylates Ser329 of DNAM-1 and plays a critical role for both DNAM-1 adhesion and signaling.
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PMID:Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. 971 30

Data from the literature indicate that ICAM-1 molecules play an important role in keratinocyte interactions with lymphocytes via the lymphocyte function-associated-1 lymphocyte-adhesion molecule. We examined the role of beta1 integrins in keratinocyte-lymphocyte adhesion under different activation conditions. Among the beta1 integrins expressed on keratinocytes and lymphocytes detected by indirect immunofluorescence microscopy and flow cytofluorometry, primarily the alpha2 and the alpha3 subunits on both cell types were involved in keratinocyte-lymphocyte adhesion. Moreover, the highest adhesion level was observed when both cell types were activated by IFN-gamma for keratinocytes and phorbol 12-myristate 13-acetate for lymphocytes, suggesting that the former involved the protein kinase C pathway. Keratinocyte activation, characterized by the expression of ICAM-1, a decrease of beta1 integrins, and the absence of alpha5beta1 integrin, was required for optimal lymphocyte adhesion. Thus, beta1 integrins remaining at the surface of IFN-gamma-treated keratinocytes could be activated by this cytokine, and could synergize with ICAM-1 and lymphocyte function-associated-1 molecules to consolidate keratinocyte-lymphocyte adhesion.
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PMID:Integrins of the beta1 family influence keratinocyte-lymphocyte interaction. 976 48

Upon activation by antigens, helper T cells differentiate into one of several subsets, characterized by their distinct cytokine-production patterns. Among these subsets, Th1 cells are known to activate cellular immunity resulting in inflammatory response, whereas Th2 cells induce humoral and allergic responses and suppress inflammation. Th1 and Th2 effector functions and their development are attributable to their distinct cytokine expression patterns. Recent reports have demonstrated that differential expression of cell surface molecules, such as adhesion molecule and chemokine receptor, is involved in their recruitment into target tissues. It is, therefore, suggested that clarification of the mechanisms of differential gene expression in Th1/Th2 should lead to rational strategies for manipulating pathological immune responses. Activation of helper T cells mediated by the T cell receptor induces a series of biochemical events. Among them, both the activation of PKC/Ras- and CaM/CN-mediated pathways play a central role in the signal transduction of cytokine gene expression. Closer examination using non-transformed murine Th1 and Th2 clones suggested that a balance between the activities of the two signaling pathways contributes to cytokine gene expression. We propose that one of the targets of PGE2, whose effect distinguishes Th1 from Th2, resides in the downstream PKC/Ras-mediated pathway.
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PMID:[Molecular mechanism of cytokine gene expression in Th1 and Th2]. 980 Apr 75


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