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T Ulshöfer

Publications and source records attributed to T Ulshöfer.

6 recordsLinked to original sources
PubMed1998

Activation of protein kinase C alpha and/or epsilon enhances transcription of the human endothelial nitric oxide synthase gene.

In primary human umbilical vein endothelial cells (HUVECs), incubation with phorbol-12-myristate-13-acetate (PMA) enhanced basal and bradykinin-stimulated nitric oxide production. In the HUVEC-derived cell line EA.hy 926, PMA and phorbol-12,13-dibutyrate stimulated endothelial nitric oxide synthase (NOS III) mRNA expression in a concentration- and time-dependent manner. Maximal mRNA expression (3.3-fold increase) was observed after 18 hr. NOS III protein and activity were increased to a similar extent. The specific protein kinase C (PKC) inhibitors bisindolylmaleimide I (1 microM), Gö 6976 [12-(2 cyanoethyl)-6,7,12, 13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo-[3, 4-c]carbazole] (1 microM), Ro-31-8220 [3-[1-[3(amidinothio)propyl-1H-inoyl-3-yl]3-(1-methyl-1H- indoyl-3-yl) maleimide methane sulfonate] (1 microM), and chelerythrine (3 microM) did not change NOS III expression when applied alone, but they all prevented the up-regulation of NOS III mRNA produced by PMA. Of the PKC isoforms expressed in EA.hy 926 cells (alpha, beta I, delta, epsilon, eta, zeta, lambda, and mu), only PKC alpha and PKC epsilon showed changes in protein expression after PMA treatment. Incubation of EA.hy 926 cells with PMA for 2-6 hr resulted in a translocation of PKC alpha and PKC epsilon from the cytosol to the cell membrane, indicating activation of these isoforms. After 24 hr of PMA incubation, both isoforms were down-regulated. The time course of activation and down-regulation of these two PKC isoforms correlated well with the PMA-stimulated increase in NOS III expression. When human endothelial cells (ECV 304 or EA.hy 926) were transiently or stably transfected with a 3.5-kb fragment of the human NOS III promoter driving a luciferase reporter gene, PMA stimulated promoter activity up to 2.5-fold. On the other hand, PMA did not change the stability of the NOS III mRNA. These data indicate that stimulation of PKC alpha, PKC epsilon, or both by active phorbol esters represents an efficacious pathway activating the human NOS III promoter in human endothelium.

Biological Transport↗
PubMed1996

Color-coded Doppler sonography in the diagnosis of abdominal masses.

A man in his forties was operated on for testicular cancer on the right-side with subsequent radiotherapy. Two years later, another tumor was found on the opposite side and surgically removed, followed by polychemotherapy. In the follow-up period, CT scanning and ultrasound showed large abdominal masses which were suspected to be metastases. Before initiating four cycles of chemotherapy, we checked their nature by Doppler sonography and found them to be recently developed abdominal varices due to an alcoholic liver cirrhosis. We were able to demonstrate that Doppler sonography can provide further information and is easy to use.

Abdomen↗
PubMed1990

Glycosaminoglycan-mediated leuserpin-2/thrombin interaction. Structure-function relationships.

Two recently identified structural elements important for glycosaminoglycan-mediated activation of human leuserpin-2 (hLS2) were investigated in detail by functional analysis of variants secreted by transiently transfected COS cells. Highly specific requirements with respect to the nature of the involved amino acids as well as to their spatial arrangements were found to be crucial for efficient activation of hLS2 by dermatan sulfate. In contrast, binding and activation of hLS2 by heparin seem to be determined mainly by the positive charge density of the involved inhibitor segment. A dimeric repeat enriched in acidic amino acids turned out to exert a dual role with respect to structure and function of hLS2. First, in the absence of functional activators the negatively charged dimer interacts intramolecularly with the glycosaminoglycan-binding site. Second, the acidic dimer is instrumental in glycosaminoglycan-mediated activation of hLS2. The monomers constituting the acidic dimer are functionally not equivalent.

Amino Acid Sequence↗
PubMed1990

On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans.

Human leuserpin-2 (hLS2) cDNA variants generated by site-directed mutagenesis were expressed in a transient COS cell system. Functional analysis of the mutants revealed two regions in the NH2-terminal half of hLS2 which are essential for glycosaminoglycan-enhanced thrombin inhibition by hLS2. One of these regions, which encompasses a dimeric structure enriched in basic amino acids, is required for both glycosaminoglycan binding and glycosaminoglycan-mediated acceleration of thrombin inhibition. Deletion of another dimeric region, which spans a sequence with a high negative charge density, resulted in a strong reduction in the glycosaminoglycan-enhanced activity of hLS2. This polyanionic region displays structural and functional similarities to the COOH-terminal end of hirudin, another potent thrombin inhibitor, indicating that both inhibitors may have a common binding site on thrombin. Based on our observations we propose a model for the activation of hLS2 by glycosaminoglycans. The key feature of this model is the suggestion that the glycosaminoglycan-enhanced reaction between hLS2 and thrombin is mediated by at least two regions of contact, involving both the reactive center region and the acidic domain of hLS2. Binding of glycosaminoglycans to hLS2 is suggested to result first in the release of the acidic region from intramolecular interactions. Then, amino acid sequences in thrombin are proposed to interact with the acidic dimer of hLS2.

Amino Acid Sequence↗