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T Noll

Publications and source records attributed to T Noll.

60 records · Page 4Linked to original sources
PubMedDate not supplied

The role of physiological oxygen partial pressures in lipid peroxidation. Theoretical considerations and experimental evidence.

The oxidative breakdown of membrane lipids, i.e. lipid peroxidation, is considered to be decisively involved in a number of toxicological and pathological processes including liver injury caused by iron overload and halogenated alkanes such as CCl4. Within the physiological oxygen partial pressure (PO2) range, i.e. at PO2 between 1 and 100 mmHg, lipid peroxidation depends on O2 in a complex manner. For instance, CCl4-induced lipid peroxidation exhibits a distinct maximum at PO2 of around 7 mmHg, and iron-induced lipid peroxidation shows marked differences in its O2 dependence between an early lag phase and a later phase of self-accelerating propagation. The O2 dependence of lipid peroxidation is either determined by the O2 dependence of initiation or the O2 dependence of propagation. Factors decisive for this are presented and the underlying alterations in the pattern of the peroxidation-related reactions delineated.

Animals↗
PubMedDate not supplied

Blockade of Ca2+-activated K+ channels inhibits proliferation of human endothelial cells induced by basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 +/- 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25-100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25-100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (-41%) and 100 nmol/l (-50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.

Calcium↗
PubMedDate not supplied

Significance of nitric oxide and peroxynitrite in permeability changes of the retinal microvascular endothelial cell monolayer induced by vascular endothelial growth factor.

Reactive oxygen species (ROS) play an important role in signaling pathways stimulated by growth factors in vascular cells. We investigated whether vascular endothelial growth factor (VEGF), which is upregulated in diabetic retinopathy and atherosclerosis, is able to enhance production of ROS, and if so, whether ROS modulate endothelial permeability. ROS levels in bovine retinal microvascular endothelial cells (BMEC) were measured by the oxidation of 2', 7'-dichlorodihydrofluorescein (DCHF), and permeability was examined by monitoring the passage of albumin through BMEC monolayers. VEGF stimulated oxidation of DCHF in BMEC, an effect which was inhibited by superoxide dismutase (SOD) and the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), but not by D-NAME. Urate, a scavenger of peroxynitrite, attenuated the VEGF-induced oxidation of DCHF. VEGF elicited a significant increase in the macromolecule permeability of BMEC monolayers within 30 min. SOD did not modify the basal or the VEGF-stimulated hyperpermeability, but the combination of SOD and VEGF induced a transient reduction in permeability after 10 min. L-NAME, but not D-NAME, enhanced VEGF-induced hyperpermeability without affecting basal values. Urate did not modify the VEGF-induced changes in permeability. In conclusion, VEGF stimulates oxidation of DCHF, which most likely represents peroxynitrite formation, and induces an increase in permeability of BMEC monolayers. Activation of NO synthase seems to counteract this stimulatory effect of VEGF on endothelial permeability.

Animals↗
PubMedDate not supplied

Heterogeneity of signal transduction mechanisms in human basophils and human skin mast cells. II. Effects of 7-O-methyl-UCN-01, NPC 15437 and bryostatin 1 and 2, four protein kinase C-modulatory agents, on mediator release.

Basophils and mast cells play a crucial role in immunological and allergic processes due to the release of inflammatory mediators such as histamine. It has been suggested for a long time that the histamine release (HR) from these cells is closely related to protein kinase (PKC) activity. However, the distinct role of PKC with its large variety of isozymes in different cell types and the actions of these isozymes in HR still remain unclear. Therefore, in the present study, we compared the effects of the two PKC inhibitors 7-O-methyl-UCN-01 (UCN-01-Me) and NPC 15437 as well as two PKC activators, bryostatin 1 and 2, on anti-IgE and Ca(2+)-ionophore-induced HR from human basophils and isolated human skin mast cells (HSMC). In both HSMC and basophils, anti-IgE-induced HR was inhibited by PKC inhibitor UCN-01-Me pre-incubation dose-dependently. In stark contrast, A23187-induced HR was unaffected by UCN-01-Me in both cell types. In our experiments, the inhibitory efficacy of the compound NPC 15437 on HR was much lower than that of UCN-01-Me and showed no statistical significance. Both bryostatins 1 and 2 produced good dose-dependent inhibition of HR from HSMC stimulated with anti-IgE, whereas HR from basophils was potentiated with these compounds. The same effects were observed with basophils stimulated with A23187, where potentiation of HR was up to fourfold of the control at the highest concentrations of bryostatins, while HSMC showed a slight decrease in HR compared to non-bryostatin-treated controls. Basophils and HSMC showed very clear differences in HR when directly stimulated with the bryostatins, since no HR was observed from HSMC while in basophils the HR increased up to 47% of total histamine at the highest concentrations of bryostatins (1 mumol/l). HR from basophils was observed to be strictly dose-dependent. The differences in the cell reactions of the two cell types incubated with these four compounds indicate distinct biochemical roles of PKC in the cascades leading to degranulation of the cells. Furthermore, the experiments with UCN-01-Me support the hypothesis of PKC-beta to play a substantial positive modulatory role for the degranulation of immunologically stimulated basophils.

Alkaloids↗