Extracellular calcium sensing in rat aortic vascular smooth muscle cells

Extracellular calcium (Ca(2+)(o)) can act as a first messenger in many cell types through a G protein-coupled receptor, calcium-sensing receptor (CaR). It is still debated whether the CaR is expressed in vascular smooth muscle cells (VSMCs). Here, we report the expression of CaR mRNA and protein in rat aortic VSMCs and show that Ca(2+)(o) stimulates proliferation of the cells. The effects of Ca(2+)(o) were attenuated by pre-treatment with MAPK kinase 1 (MEK1) inhibitor, as well as an allosteric modulator, NPS 2390. Furthermore, stimulation of the VSMCs with Ca(2+)(o)-induced phosphorylation of ERK1/2, but surprisingly did not cause inositol phosphate accumulation. We were not able to conclusively state that the CaR mediates Ca(2+)(o)-induced cell proliferation. Rather, an additional calcium-sensing mechanism may exist. Our findings may be of importance with regard to atherosclerosis, an inflammatory disease characterized by abnormal proliferation of VSMCs and high local levels of calcium.     

Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes

Both intra- and extracellular calcium play multiple roles in the physiology and pathophysiology of cardiomyocytes, especially in stimulus-contraction coupling. The intracellular calcium level is closely controlled through the concerted actions of calcium channels, exchangers, and pumps; however, the expression and function(s) of the so-called calcium-sensing receptor (CaR) in the heart remain less well characterized. The CaR is a seven-transmembrane receptor, which, in response to noncovalent binding of extracellular calcium, activates intracellular effectors, including G proteins and extracellular signal-regulated kinases (ERK1/2). We have shown that cultured neonatal cardiomyocytes express the CaR messenger RNA and the CaR protein. Furthermore, increasing concentrations of extracellular calcium and a type II CaR activator "calcimimetic" caused inositol phosphate (IP) accumulation, downregulated tritiated thymidine incorporation, and supported ERK1/2 phosphorylation, suggesting that the CaR protein is functionally active. Interestingly, the calcimimetic induced a more rapid ERK1/2 phosphorylation than calcium and left-shifted the IP concentration-response curve for extracellular calcium, supporting the hypothesis that CaR is functionally expressed in cardiac myocytes. This notion was underscored by studies using a virus containing a dominant-negative CaR construct, because this protein blunted the calcium-induced IP response. In conclusion, we have shown that the CaR is functionally expressed in neonatal ventricular cardiomyocytes and that the receptor activates second messenger pathways, including IP and ERK, and decreases DNA synthesis. A specific calcium-sensing receptor on cardiac myocytes could play a role in regulating cardiac development, function, and homeostasis.     

Discrimination between enantiomers of linalool by olfactory receptor neurons in the cabbage moth Mamestra brassicae (L.)

Plants emit complex blends of volatiles, including chiral compounds that might be detected by vertebrates and invertebrates. Insects are ideal model organisms for studying the underlying receptor neuron mechanisms involved in olfactory discrimination of enantiomers. In the present study, we have employed two-column gas chromatography linked to recordings from single olfactory receptor neurons of Mamestra brassicae, in which separation of volatiles in a polar and a chiral column was performed. We here present the response properties of olfactory receptor neurons tuned to linalool. The narrow tuning of these receptor neurons was demonstrated by their strong responses to (R)-(-)-linalool, the weaker responses to the (+)-enantiomer as well as a few structurally related compounds, and no responses to the other numerous plant released volatiles. The enantioselectivity was verified by parallel dose-response curves, that of (R)-(-)-linalool shifted 1 log unit to the left of the (S)-(+)-linalool curve. A complete overlap of the temporal response pattern was found when comparing the responses of the same strength. Analysis of the spike amplitude and waveform indicated that the responses to the two enantiomers originated from the same neuron.     

Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery

Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.     

Sequencing the genome of the Atlantic salmon (<Emphasis Type="Italic">Salmo salar</Emphasis>)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids.     

Phenomics: the next challenge

A key goal of biology is to understand phenotypic characteristics, such as health, disease and evolutionary fitness. Phenotypic variation is produced through a complex web of interactions between genotype and environment, and such a 'genotype-phenotype' map is inaccessible without the detailed phenotypic data that allow these interactions to be studied. Despite this need, our ability to characterize phenomes - the full set of phenotypes of an individual - lags behind our ability to characterize genomes. Phenomics should be recognized and pursued as an independent discipline to enable the development and adoption of high-throughput and high-dimensional phenotyping.     

Carotenoid dynamics in Atlantic salmon

Background  

Carotenoids are pigment molecules produced mainly in plants and heavily exploited by a wide range of organisms higher up in the food-chain. The fundamental processes regulating how carotenoids are absorbed and metabolized in vertebrates are still not fully understood. We try to further this understanding here by presenting a dynamic ODE (ordinary differential equation) model to describe and analyse the uptake, deposition, and utilization of a carotenoid at the whole-organism level. The model focuses on the pigment astaxanthin in Atlantic salmon because of the commercial importance of understanding carotenoid dynamics in this species, and because deposition of carotenoids in the flesh is likely to play an important life history role in anadromous salmonids.     

The effect of long-chain alkyl betainates on the arylesterase-like activity of bovine serum albumin

The effect of a hydrolyzable cationic surfactant, tetradecyl betainate (tetradecyloxycarbonyl-N,N,N-trimethylmethanaminium chloride), on the arylesterase-like activity of bovine serum albumin (BSA) was investigated. The rate of hydrolysis of p-nitrophenyl hexanoate in the presence of BSA and varying concentrations of the surfactant was followed. The rate was found to be dependent on the concentration of the cationic surfactant and a maximum was found in the curve at ca. 3 m . The Michaelis-Menten constants (K_m/n, where n is the number of active sites) and the “catalytic” rate constants (k₂) were determined for the reactions, and were found to be 11 and 40 times larger, respectively, in the presence of the surfactant. The hydrolysis of radiolabeled tetradecyl betainate in the presence and absence of BSA was also followed. This study, together with a binding study based on gel permeation chromatography, showed that the surfactant binds to the protein, but that no hydrolysis of the betaine ester takes place while bound to BSA. It was thus concluded that the increased value of k₂ in the presence of a cationic surfactant was not, as has been previously suggested, due to an increased local hydroxide concentration resulting from the formation of a new pseudophase.