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Martina Weber

Publications and source records attributed to Martina Weber.

8 recordsLinked to original sources
PubMed2003

Diethyldithiocarbamate inhibits the catalytic activity of xanthine oxidase.

We sought to determine the effects of the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC) on vascular superoxide production. Rat aortic rings treated with DETC (10 mM) showed no change of superoxide generation (5 microM lucigenin). Likewise, DETC did not change the expression and activity of vascular soluble guanylyl cyclase, an enzyme known to be extremely sensitive to superoxide. In striking contrast, DETC completely inhibited the superoxide production induced by 6-anilino-5,8-quinolinedione (LY83583) and abolished the catalytic activity of xanthine oxidase (XO). Thus, DETC inhibits vascular superoxide production by blocking oxidoreductase enzymes such as XO and those reducing LY83583 in rat aorta.

Aminoquinolines↗
PubMed2003

The effect of hypercholesterolemia on platelet soluble guanylyl cyclase.

We sought to determine whether hypercholesterolemia impacts on the NO-stimulated activity of platelet soluble guanylyl cyclase (sGC). We investigated two groups of nine New Zealand white rabbits receiving either a standard (NC) or a cholesterol chow (HC, 0.75%) for 15 weeks. The plasma content of cGMP and the specific activity of sGC in intact platelets were measured by a cGMP-specific radioimmunoassay. In HC, 47.9+/-3.1% of the aortic intimal area was covered with atherosclerotic lesions, and plasma cGMP levels (pmol/ml) were increased from 12.6+/-1.2 to 27.9+/-3.5 (P<.0001). In striking contrast, hypercholesterolemia had no effect on sGC activity stimulated by the NO donor SNAP. At 100 microM SNAP, the specific activities of sGC (pmol/10(9) platelets/min) were 81.8+/-14.5 in NC and 86.2+/-8.1 in HC. Basal sGC activity (pmol/10(9) platelets/min) was also similar in NC (0.21+/-0.04) and HC (0.460+/-0.11, P=.7813). In accordance, washed platelets from both groups showed a similar SNAP-induced inhibition of aggregation. These data suggest that an impaired response of platelets to NO is most likely not involved in platelet hyperreactivity in hypercholesterolemia.

Animals↗
PubMed2002

Olfactory receptor expressed in ganglia of the autonomic nervous system.

Certain members of the olfactory receptor superfamily appear to be expressed not only in chemosensory neurons of the nasal epithelium. Analyzing the transgenic mouse line MOL2.3-IGITL, the olfactory receptor subtype MOL2.3 was found to be expressed in distinct subpopulations of cells within a cranial, a cervical as well as within a thoracic ganglion. By means of coexpressed markers, the axonal processes of MOL2.3 expressing cells could be visualized and thus the target tissues innervated by these ganglionic neurons identified. Stained fibers, but no stained cell bodies were visible in distinct head regions, notably in the lateral nasal gland and in the so-called Harderian gland; staining was also observed on distinct segments of blood vessels, especially within the tongue. In the thoracic region, the heart and a small segment of the aorta as well as a distinct population of lung alveoli were labeled by incoming blue fibers. Expression of MOL2.3 in cells of the autonomic nervous system supports the idea that at least some of the multiple olfactory receptor types serve functions others than odorant detection.

Animals↗
PubMed2002

Tracking the immunoregulatory mechanisms active during allograft tolerance.

Immunoregulatory mechanisms dependent on regulatory CD4+ T cells are believed to be critical in the maintenance of peripheral tolerance to allografts. However, a detailed characterization of the effects of these regulatory T cells has been hampered by the absence of a simple means to track and study them. In this work we provide evidence that in a murine model of islet transplantation the interactions between alloaggressive and regulatory T cells can be studied in vitro and in vivo at the single-cell level. The observations made in both an in vitro coculture system and an in vivo CFSE-based adoptive transfer model indicate that lymphocytes from tolerant allograft recipients 1) proliferate weakly to donor strain allogeneic cells but vigorously to third-party strain cells; and 2) suppress the proliferation of naive syngeneic CD4+ and CD8+ T cells to donor tissue in a cell dose- and Ag-specific manner. These effects depend on the presence of CD4+CD25+ T cells and are neutralized by anti-CTLA4 mAb or rIL-2. The principal effect of anti-CTLA4 is directed against the naive, not regulatory, T cell population. These results can be replicated in vivo by transferring lymphocyte populations into transplant recipients, proving that the graft-protecting actions of regulatory T cells are blunted by a rise in the number of allodestructive T cells (pool size model) and depend on the presence of CD4+CD25+ T cells and the integrity of the CTLA4/B7 pathway.

Abatacept↗
PubMed2002

Effect of hypercholesterolemia on expression and function of vascular soluble guanylyl cyclase.

BACKGROUND: Vasorelaxation to endothelial NO is mediated by activation of soluble guanylyl cyclase (sGC) and impaired by hypercholesterolemia in animals and humans. We investigated whether hypercholesterolemia impacts expression and function of sGC. METHODS AND RESULTS: White New Zealand rabbits (n=10 per group) received a standard diet for 16 weeks (SD16) (n=20) or 32 weeks (SD32) and a cholesterol diet (7.5 g/kg) for 16 weeks (CD16) (n=20) or 32 weeks (CD32), respectively. Another group received cholesterol diet for 16 weeks followed by standard diet for 16 weeks (CD/SD). Aortic expression of the alpha1-subunit of sGC (sGC-alpha1) and beta1-subunit of sGC (sGC-beta1) was assessed by Western blot. Function was measured by aortic relaxation to S-Nitroso-N-acetyl-D, L-penicillamine (SNAP) and sGC activity in aortic cytosols. Hypercholesterolemia induced an upregulation of sGC-beta1 in CD16 (3.5+/-0.4-fold, P<0.001 versus SD16) and CD32 (4.0+/-0.4-fold, P<0.001 versus SD32). A similar increase was found for sGC-alpha1. In striking contrast, basal and NO-stimulated sGC activities in aortic cytosols of CD16 were only slightly enhanced (1.4-fold, P<0.05). Furthermore, the vasodilator potency of SNAP (EC50 in -logM) was 10-fold lower in CD16 (6.76a+/-0.09) than in SD16 (7.66+/-0.14, P<0.01). The increase of sGC expression was completely reversible, as indicated by comparable sGC-beta1 amounts in SD32 and CD/SD (1.2+/-0.1-fold, P>0.05). Immunohistochemical analysis suggests that a great portion of the overexpressed sGC is located in intimal lesions. Additional experiments showed that increased vascular superoxide production induced by 6-anilino-5,8-quinolinedione (LY85385) reduces sGC-activity but increases sGC-expression. CONCLUSIONS: These results suggest that hypercholesterolemia induces a reversible overexpression of a dysfunctional vascular sGC, which may contribute to the pathogenesis of atherosclerosis.

Aminoquinolines↗