A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction

Abstract: BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B2 receptors (B2R). BbKI was examined on smooth muscle contraction and Ca2+ mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca2+]cand contraction, as observed with BK (2.0 μm). Not blocked by B1 receptors (B1R), the BbKI agonistic effect was blocked by the B2R antagonist, HOE-140 (6 μm), and the involvement of B2R was confirmed in B2R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca2+ release from internal storages, as a consequence of its interaction with B2R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B2R involvement.     

A role for CDK9 in UV damage response

Comment on: Shchebet A, et al. Cell Cycle 2012; 2122-7     

Social Environment Affects Acquisition and Color of Structural Nuptial Plumage in a Sexually Dimorphic Tropical Passerine

Structural colors result from the physical interaction of light with organic materials of differing refractive indexes organized at nanoscale dimensions to produce significant interference effects. Because color properties emerge from these finely organized nanostructures, the production of structural coloration could respond to environmental factors and be developmentally more plastic than expected, functioning as an indicator of individual quality. However, there are many unknown factors concerning the function and mechanisms regulating structural coloration, especially relative to social environment. We hypothesized that social environment, in the form of competitive settings, can influence the developmental pathways involving production of feather structural coloration. We experimentally assessed the impact of social environment upon body condition, molt and spectral properties of two types of structural color that compose the nuptial plumage in blue-black grassquits: black iridescent plumage and white underwing patches. We manipulated male social environment during nine months by keeping individuals in three treatments: (1) pairs; (2) all-male groups; and (3) male-female mixed groups. All morphological characters and spectral plumage measures varied significantly through time, but only acquisition of nuptial plumage coverage and nuptial plumage color were influenced by social environment. Compared with males in the paired treatment, those in treatments with multiple males molted into nuptial plumage faster and earlier, and their plumage was more UV-purple-shifted. Our results provide experimental evidence that social context strongly influences development and expression of structural plumage. These results emphasize the importance of long-term experimental studies to identify the phenotypic consequences of social dynamics relative to ornament expression.     

Secretome of HepG2 cells infected with dengue virus: implications for pathogenesis

Viral hemorrhagic fever is a clinical syndrome that poses serious global health threat. Among the causative agents, dengue virus (DV) has the highest incidence rate and its infection is the major cause of viral hemorrhagic fever in the world. Although the pathophysiological mechanisms of DV-induced diseases are not yet understood, it is well accepted that liver is a site of viral replication. In this study, we used proteomics to analyze infection of a hepatic cell lineage, HepG2, with DV, focusing on the secreted proteins. 1D-electrophoresis and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were used, allowing the identification of a total of 107 proteins, among which 35 were found only in control secretome and 24 only in infected cells secretome. To validate these data, we performed 2D-eletrophoresis followed by MALDI-TOF/TOF, resulting in the identification of 20 proteins, 8 of them confirming LC-MS/MS results. We discuss the results obtained taking into account the proteins previously described in the secretome of HepG2 cells, proteins present in human plasma and proteins of interest for dengue pathogenesis. Altogether the data presented here provide clues for the progress in the understanding of the role of liver secretion in the progression of the disease.     

Histocompatibility antigens (HLA) in children with lipoid nephrosis]

Actual knowledge on the HLA relationship with the primary glomerulopathies, with particular reference to steroid - sensitive nephrosis of childhood, is surveyed. Occurrence of HLA B-8 and B-35 in this nephropathy has been investigated. The studies involved 47 patients aged between 3 and 15 years and 117 healthy children from Lower Silesian region. It has been showed, that HLA B-8 is present more frequently in sick children, than in healthy controls. The situation is reverse in case of HLA B-35 antigen. However, the difference is statistically insignificant. A probability of the lipid nephrosis sensitivity to corticosteroids can not be predicted on the base of the presence of these HLA antigens.     

Muscarinic receptors in pineal

The presence of muscarinic receptors in sheep and rat pineals was detected by binding of [³H]quinuclidinyl benzilate ([³H]QNB), a potent and specific muscarinic antagonist. [³H]QNB binding to sheep pineal membrane resuspensions was saturable and reversible, with a rate constant for association at 37°C of 6×10⁸M^?1min^?1 and a rate constant for dissociation of 1×10^?2min^?1. Kinetic and saturation experiments yielded an equilibrium dissociation constant of 13–18 pM and a concentration of binding sites equivalent to 1.1 pmol/g of original wet weight. This is only about 5% of the level of β-adrenergic receptors. Competition by a variety of cholinergic drugs confirmed the muscarinic nature of the binding sites. Experiments in rats failed to detect a significant decrease in pineal [³H]QNB binding following bilateral superior cervical ganglionectomy, suggesting that the binding sites are not localized exclusively on sympathetic terminals.     

The Protective Action of Rubus sp. Fruit Extract Against Oxidative Damage in Mice Exposed to Lipopolysaccharide

Neurochemical Research - Neuroinflammation is an event that occurs in several pathologies of brain. Rubus sp. (blackberry) is a powerful antioxidant fruit, and its extract has neuroprotective...