The source of heme for vascular heme oxygenase I: heme uptake in rat aorta

During the last decade, heme oxygenase (HO) and carbon monoxide (CO) have garnered substantial research interest in terms of cell and organ regulation, especially as they bear on the central nervous system, organ transplantation, and the cardiovascular system. While the enzymatic mechanism, substrates, and products of HO are well known, it is not clear whether the cardiovascular system derives its supply of the heme substrate through de novo synthesis or uptake from the extracellular milieu. The objective of the present study was to test the latter possibility in rat aorta and to determine the influence of plasma proteins that bind heme in vivo, viz. hemopexin and albumin. Aortic tissue was exposed to [14C]heme in vitro, and the concentration and time dependence of heme uptake was assessed. The presence of hemopexin or albumin in the incubation medium dramatically decreased heme uptake by the aorta. Heme uptake by aortic tissue was not altered after induction of HO-1, which would be expected to increase tissue heme demand. In summary, the rat, isolated aorta was capable of obtaining heme from its external milieu, but this was obtunded in the presence of the plasma proteins hemopexin or albumin. For normal physiological situations, heme uptake may not be a usual source of substrate for vascular HO and hemoenzymes such as nitric oxide synthase, soluble guanylyl cyclase, and cyclooxygenase.     

Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7beta1 and dystroglycan

Transgenically introduced laminin (LN) alpha1 chain prevents muscular dystrophy in LNalpha2 chain deficient mice. We now report increased integrin alpha7Bbeta1D synthesis in dystrophic LNalpha2 chain deficient muscle. Yet, immunofluorescence demonstrated a reduced expression of integrin alpha7B subunit at the sarcolemma. Transgenic expression of LNalpha1 chain reconstituted integrin alpha7B at the sarcolemma. Expression of alpha- and beta-dystroglycan is enhanced in LNalpha2 chain deficient muscle and normalized by transgenic expression of LNalpha1 chain. We suggest that LNalpha1 chain in part ameliorates the development of LNalpha2 chain deficient muscular dystrophy by retaining the binding sites for integrin alpha7Bbeta1D and alpha-dystroglycan, respectively.     

Salicylic acid - a potential biomarker of tobacco Bel-W3 cell death developed as a response to ground level ozone under ambient conditions

Salicylic acid content and benzoic acid 2-hydroxylase (BA2H) activity were investigated in tobacco Bel-W3 and Bel-B leaves after exposure to tropospheric ozone in the conditions of ambient air. Plants were exposed in accordance with a standard methodology for ozone biomonitoring, in a three-year experiment. Free salicylic acid (SA), conjugated with glucose (SAG), and as a product of the BA2H activity was quantified with HPLC. In order to evaluate ozone injuries of leaves, an open source image analysis software was employed. Plants exposure to ambient ozone resulted in enhanced BA2H activity and intensified salicylic acid biosynthesis in leaves of Bel-W3 cultivar showing visible ozone injuries. The BA2H activity significantly correlated with SAG for ozone-exposed Bel-W3 plants. Both injuries and salicylic acid biosynthesis rate depended on the growth phase of leaves and nearly linear correlation between SA content and injuries was found for particular leaves of Bel-W3.     

Comparison of pharmacological properties of rubidomycine and its newly synthesized derivatives DR-22 and DR-27 in animals

The effect of two newly synthesized 5-amino modified analogues of rubidomycine was submitted to preliminary pharmacological and histological investigations in healthy Albino Swiss mice. The results showed a similarity of the tested properties of the new compounds and commercial rubidomycine, suggesting the same spectrum undesired side-effects after acute administration. Of the two novel compounds DR-22 was found to be less toxic, while much potent in its action on the haematopoietic system in comparison to rubidomycine, in prolonged treatment. DR-22 is a candidate for further, more detailed investigations.     

Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion

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Anatomical changes in the structure of the temporomandibular joint caused by complete edentulousness

doi: 10.1111/j.1741‐2358.2011.00498.x
Anatomical changes in the structure of the temporomandibular joint caused by complete edentulousness Background: The posterior slope of the articular eminence of completely edentulous patients compared to patients with maintained occlusion shows significant flattening. Objective: The aim of this present study was to reveal a possible correlation between edentulousness and the flattening of the eminence and to find out whether this deformation is connected to age. Material and methods: Thirty patients were examined in three groups, each consisting of 10 persons (group I: 18‐ to 25‐year‐old patients with maintained occlusion, group II: patients over 60 with maintained occlusion, group III: edentulous patients over 60). The three groups were compared according to dental status, age, sex and side. Measurements were carried out on orthopantomographic images taken with Kodak 8000 Digital Panoramic System. The angle of the posterior slope of the articular eminence relative to the Frankfort plane was measured on both sides. Data were analysed statistically with the one‐way anova test (α = 0.05). Results: The highest values were measured in group I (right side: 39.8 ± 5.4°, left side: 43.0 ± 5.9°), values were somewhat lower in group II (right side: 38.9 ± 4.7°, left side: 39.5 ± 7.4°) and were the lowest in group III, which was significantly lower on both sides than the results of group I and group II (right side: 29.8 ± 6.0°, left side: 31.9 ± 5.2°, p < 0.01). The correlation coefficient between age and the flattening of the eminence in group I, II and III was 0.23, 0.35 and 0.92, respectively. Conclusion: The flattening of the articular eminence could be correlated with age; however, the rate of deformation is significantly higher in completely edentulous patients than in patients with maintained occlusion.     

Influence of the polyphenolic tannic acid on the toxicity of the insecticide deltametihrin to fish. A comparative study examining both biochemical and cytopathological parameters

Humics and pesticides are present in aquatic environment and the toxicological consequences of their chemical interaction is well studied. However, data concerning the mechanism of the biochemical action of humic-pesticide combinations are scarce, especially in vertebrates. Thus we have chosen to study the in vivo effects of the plant polyphenolic tannic acid and the pyrethroid insecticide deltamethrin [Decis] alone or in combination on hepatic xenobiotic-metabolizing enzyme activities and the associated redox-parameters in carp, as the complex assessment of these systems are regarded to serve as a relevant biomarker of environmental pollution. Stress effects and tissue damage were followed by determination of the plasma glucose level, the activities of plasma transaminases, and by electron microscopy. Tannic acid alone exerted weak prooxidant effect due to its marked antioxidant enzyme inhibitory activity. Deltamethrin, applied in a very low dose, induced oxyradical production in fish via activation of cytochrome P450 isozymes. This effect was promoted by the antioxidant enzyme inhibitory action of tannic acid, when the two chemicals were combined; however, the ultrastructural damage of the hepatocytes was reduced by the common cytoprotective capacity of the phenolic. Numerous humics are known to alter the toxicity of pesticides and their influence depends on their type and concentration. Therefore, our work taken together with other comparative studies may contribute to the assessment of the impact of humics in nature, especially in case of environmental pollution.     

The source of heme for vascular heme oxygenase II: de novo heme biosynthesis in rat aorta

Heme is an essential prosthetic group or substrate for many proteins, including hemoglobin, and hemo enzymes such as nitric oxide synthase, soluble guanylyl cyclase, and heme oxygenase (HO). HO is responsible for the breakdown of heme into equimolar amounts of biliverdin, iron, and carbon monoxide, the latter of which is thought to play a role in the regulation of vascular tone. It is not clear whether the source of heme for cardiovascular functions is derived from uptake from the extracellular milieu or synthesis. In this study, we tested the hypothesis that blood vessels obtain their supply of heme for HO through de novo synthesis. Adult male Sprague-Dawley rat aorta was incubated at 37 degrees C in Krebs' solution with 1 micro M [14C]delta-aminolevulinic acid (ALA). [14C]ALA uptake was linear for about 30 min and reached a plateau at approximately 100 min. The radioactivity was incorporated into porphyrins and heme as determined by esterification of 14C-labelled metabolites and thin-layer chromatography. The first and rate-limiting step of heme biosynthesis is catalyzed by ALA synthase (ALA-S), the activity of which was determined in rat aorta using a radiometric assay, approximately 250 nmol x (g wet mass)(-1) x h(-1). Inducing HO-1 in rat aorta with S-nitroso-N-acetylpenicillamine (500 micro M) did not increase ALA-S activity as compared with basal activity levels of the enzyme. It appears that there is a sufficient amount of heme available under basal ALA-S activity conditions to meet the increased demand for heme resulting from HO-1 induction. These observations indicate that the complete enzymatic pathway for de novo heme biosynthesis resides in rat aorta and furthermore indicate that de novo heme synthesis is capable of supplying a substantial portion of the heme substrate for HO in the aorta.