Biomedical subjects

H Røshol

Publications and source records attributed to H Røshol.

3 recordsLinked to original sources

PubMed1997

DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion.

DOC2 proteins constitute a novel protein family that may function in secretion and contain a double C2 domain. We have cloned and characterized two DOC2 isoforms in rat brain and studied their interactions with other proteins implicated in secretion. DOC2A was virtually brain specific, DOC2B ubiquitous. Within brain, the isoforms were expressed nonuniformly and complementary within neurons, not astroglia, and copurified with synaptic vesicles. Affinity purification, yeast two-hybrid analysis, and coimmunoprecipitation revealed that DOC2 binds munc18, a protein also implicated in secretion. The first DOC2 C2 domain and most of munc18 are involved in direct interactions. Munc18 may regulate formation of 'core complexes' during vesicle docking, by interacting with syntaxin. We show that DOC2 and syntaxin compete for munc18. Other core complex components shifted the equilibrium between syntaxin-munc18 versus DOC2-munc18. These data suggest that DOC2 proteins are vesicular adapter proteins regulating munc18-syntaxin complexes and herewith synaptic vesicle docking.

Amino Acid Sequence↗

PubMed1996

Peritoneal leucocytes from spontaneously hypertensive rats have reduced chemiluminescence response and lowered sensitivity to dexamethasone in vivo.

The genetically altered hypothalamo-pituitary-adrenocortical axis in the spontaneously hypertensive rat (SHR) suggests altered phagocyte function in this strain. We therefore compared luminol-amplified chemiluminescence in peritoneal leucocytes from 10- to 12-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs) activated by serum-opsonized zymosan particles (SOZ), N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). While the number of peritoneal monocytes/macrophages was increased by 49% in SHRs relative to WKYs, activator-induced chemiluminescence per cell in SHRs was only 14-42% of that in WKYs. FMLP responses were especially low in SHRs. Treatment of rats with dexamethasone in the drinking water for 48 h prior to ex vivo experiments reduced chemiluminescence dose-dependently in WKYs as well as in SHRs. ED50 of dexamethasone in SHRs was, however, increased compared to WKYs, indicating lowered sensitivity to dexamethasone in SHRs. No evidence was found of strain differences in differential distribution of peritoneal cells or in pharmacokinetics of dexamethasone. Plasma ACTH levels were significantly higher in SHRs than in WKYs, while basal plasma corticosterone concentrations in SHRs and WKYs were not significantly different. The results suggest that production of reactive oxygen compounds by peritoneal mononuclear phagocytes is reduced in SHRs compared with WKYs, and that the phagocyte respiratory burst is modulated differently by endogenous glucocorticoids in the two strains. We propose that reduced activity of the phagocyte NADPH oxidase-myeloperoxidase system is a major contributory cause of the altered chemiluminescence responses in SHRs. The data indicate that species differences may also be present at earlier steps in the signal transduction pathways activated by SOZ, fMLP and PMA.

Adrenocorticotropic Hormone↗

PubMed1995

Dexamethasone and methylprednisolone affect rat peritoneal phagocyte chemiluminescence after administration in vivo.

Production of reactive oxygen compounds by peritoneal monocytes/macrophages was studied in rats exposed to dexamethasone or methylprednisolone in the drinking water. Luminol-amplified chemiluminescence was measured in preparations of peritoneal leukocytes activated ex vivo by serum opsonized zymosan, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). After dexamethasone administration for 1 day (approximately 0.13 mg/kg per 24 h) a significant reduction in chemiluminescence was found in cells stimulated with serum opsonized zymosan, while responses to fMLP and PMA stimulation were significantly reduced after 2 days. The maximal inhibition obtained after 5-8 days of dexamethasone administration (plasma levels < 5 nM) was 92.0 +/- 1.2%, 87.6 +/- 0.2% and 84.5 +/- 3.1% in cells stimulated with serum opsonized zymosan, fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone for 48 h gave a dose-dependent reduction of chemiluminescence. ED50 values of dexamethasone were estimated at 0.06-0.15 mg/kg for the different stimulators (plasma concentrations 5-10 nM). Estimated ED50 values for methylprednisolone were 35-36 mg/kg. Since the percentage of mononuclear phagocytes in the peritoneal cell population did not change significantly with dose or time of dexamethasone exposure, this study indicates that glucocorticoids have a depressive effect on the monocyte/macrophage 'respiratory burst' in vivo. The results are consistent with the hypothesis that these effects are mediated by glucocorticoid receptors. Although the pathway activated by serum opsonized zymosan was more rapidly inhibited than the fMLP- and PMA-activated pathways, the responses induced by the different stimulators were similarly affected, suggesting a modulation of common components in the activation pathways, possibly protein kinase C or the NADPH-oxidase complex, after administration of low pharmacological doses of glucocorticoids in vivo.

Animals↗