1.Nitrobindin: An Ubiquitous Family of All β-Barrel Heme-proteins.
De Simone G1,2, Ascenzi P1,2, Polticelli F1,3. IUBMB Life. 2016 Apr 15. doi: 10.1002/iub.1500. [Epub ahead of print]
Rhodnius prolixus nitrophorins (Rp-NPs), Arabidopsis thaliana nitrobindin (At-Nb), and Homo sapiens THAP4 (Hs-THAP4) are the unique known proteins that use a β-barrel fold to bind ferric heme, which is devoted to NO transport and/or catalysis. The eight-stranded antiparallel β-barrel Rp-NPs, which represent the only heme-binding lipocalins, are devoted to deliver NO into the blood vessel of the host and to scavenge histamine during blood sucking. Regarding Nbs, crystallographic data suggest the ability of At-Nb and Hs-THAP4 to bind ferric heme; however, no data are available with respect to these functions in the natural host. Here, a bioinformatics investigation based on the amino acid sequences and three-dimensional structures of At-Nb and Hs-THAP4 suggests a conservation of the 10-stranded antiparallel β-barrel Nb structural module in all life kingdoms of the evolutionary ladder. In particular, amino acid residues involved in the heme recognition and in the structure stabilization of the Nb structural module are highly conserved (identity > 29%; homology > 83%).
2.Interaction Between Daidzein and Hesperetin on Antispasmodic Action in Isolated Sensitized and Non-sensitized Guinea-Pig Tracheas.
Shih CH1, Chang TY2, Ko WC2. Front Pharmacol. 2016 Mar 29;7:75. doi: 10.3389/fphar.2016.00075. eCollection 2016.
In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph.
3.When cholesterol meets histamine, it gives rise to dendrogenin A: a tumour suppressor metabolite1.
Poirot M1, Silvente-Poirot S1. Biochem Soc Trans. 2016 Apr 15;44(2):631-7. doi: 10.1042/BST20150232.
Dendrogenin A (DDA) is the first steroidal alkaloid (SA) to be identified in human tissues to date and arises from the stereoselective enzymatic conjugation of 5,6α-epoxycholesterol (5,6α-EC) with histamine (HA). DDA induces the re-differentiation of cancer cellsin vitroandin vivoand prevents breast cancer (BC) and melanoma development in mice, evidencing its protective role against oncogenesis. In addition, DDA production is lower in BCs compared with normal tissues, suggesting a deregulation of its biosynthesis during carcinogenesis. The discovery of DDA reveals the existence of a new metabolic pathway in mammals which lies at the crossroads of cholesterol and HA metabolism and which leads to the production of this metabolic tumour suppressor.
4.Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in Human endothelial cells.
da Silva ML1, O'Connor MN1, Kriston-Vizi J2, White IJ3, Al-Shawi R4, Simons JP4, Mössinger J5, Haucke V5, Cutler DF6. J Cell Sci. 2016 Apr 11. pii: jcs.187864. [Epub ahead of print]
Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Whilst many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined the role of two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody binding sites. When stimulated with histamine, these cells release normal levels of VWF, yet under flow form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls.