Presence Of Several Domains Research Articles

Molecular, immunological, and physiological evidences of a sphingosine-activated plasma membrane Ca2+-channel in Trypanosoma equiperdum.

The hemoparasite Trypanosoma equiperdum belongs to the Trypanozoon subgenus and includes several species that are pathogenic to animals and humans in tropical and subtropical areas across the world. As with all eukaryotic organisms, Ca2+ is essential for these parasites to perform cellular processes thus ensuring their survival across their life cycle. Despite the established paradigm to study proteins related to Ca2+ homeostasis as potential drug targets, so far little is known about Ca2+ entry into trypanosomes. Therefore, in the present study, the presence of a plasma membrane Ca2+-channel in T. equiperdum (TeCC), activated by sphingosine and inhibited by verapamil, is described. The TeCC was cloned and analyzed using bioinformatic resources, which confirmed the presence of several domains, motifs, and a topology similar to the Ca2+ channels found in higher eukaryotes. Biochemical and confocal microscopy assays using antibodies raised against an internal region of human L-type Ca2+ channels indicate the presence of a protein with similar predicted molar mass to the sequence analyzed, located at the plasma membrane of T. equiperdum. Physiological assays based on Fura-2 signals and Mn2+ quenching performed on whole parasites showed a unidirectional Ca2+ entry, which is activated by sphingosine and blocked by verapamil, with the distinctive feature of insensitivity to nifedipine and Bay K 8644. This suggests a second Ca2+ entry for T. equiperdum, different from the store-operated Ca2+ entry (SOCE) previously described. Moreover, the evidence presented here for the TeCC indicates molecular and pharmacological differences with their mammal counterparts, which deserve further studies to evaluate the potential of this channel as a drug target.

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Modulation in the mRNA expression of ecdysone receptor gene in aquatic midge, Chironomus riparius upon exposure to nonylphenol and silver nanoparticles

Chironomus riparius, a non-biting midge (Chironomidae, Diptera), is extensively used as a model organism in aquatic ecotoxicological studies, although little is known about its genome sequences. Ecdysteroids are steroid hormones that play an important role in development, growth, moulting of larva, and reproduction in Chironomus spp. The effect of ecdysteroids is mediated by their binding to the ecdysteroid receptor ( EcR). To study the effect of environmental stressors, nonylphenol and silver nanoparticles (AgNPs), on the modulation of EcR mRNA, in this study, full length cDNA of C. riparius ecdysone receptor ( CrEcR) was identified from the Expressed Sequence Tags (ESTs) database and expression of the corresponding mRNA was analyzed following exposure to nonylphenol and AgNPs. The CrEcR cDNA was 2548 base pairs (bp) in length, with a 5′ untranslated region (UTR) of 242 bp and a 3′ UTR of 684 bp. The open reading frame contains 1617 nucleotides, encoding 539 amino acids with a predicted molecular weight of 61 kDa and p I of 5.89, and revealed the presence of several domains associated with DNA binding, dimerization, ligand binding and transcriptional activation characteristic of steroid receptor family members. It was found that the expression level of CrEcR was significantly up-regulated on exposure to nonylphenol and significant up or down regulation was observed on exposure to AgNPs. These finding shows that nonylphenol as well as AgNPs could modulate the ecdysone nuclear receptor and may have significant implications in different developmental stages in C. riparius.