Human ether-a-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling

Adhesive receptors of the integrin family are primarily involved in cell-extracellular matrix adhesion. Additionally, integrins trigger multiple signaling pathways that are involved in cell migration, proliferation, survival, and differentiation. We previously demonstrated that the activation of integrins containing the beta(1) subunit leads to a selective increase in potassium currents carried by the human ether-a-go-go-related gene (hERG) channels in neuroblastoma and leukemia cells; this current activation modulates adhesion-dependent differentiation in these cells. We hypothesized that the cross-talk between integrins and hERG channels could be traced back to the assembly of a macromolecular signaling complex comprising the two proteins. We tested this hypothesis in both SH-SY5Y neuroblastoma cells and in human embryonic kidney 293 cells stably transfected with hERG1 and, therefore, expressing only the full-length hERG1 protein on the plasma membrane. The beta(1) integrin and hERG1 coprecipitate in these cells and colocalize in both intracellular and surface membrane compartments. The two proteins also coprecipitate with caveolin-1, suggesting the localization of the complex in lipid rafts/caveolae. hERG1-transfected cells undergo an activation of hERG currents after beta(1) integrin-mediated adhesion to fibronectin; concomitant with this activation, the focal adhesion kinase associates with the hERG1 protein and becomes tyrosine phosphorylated. Using hERG1-specific inhibitors, we show that the tyrosine phosphorylation of focal adhesion kinase is strictly dependent on hERG channel activity. Similarly, the activity of the small GTPase Rac1 turned out to be dependent on hERG currents. On the whole, these data indicate that the hERG1 protein associates with beta(1) integrins and modulates adhesion receptor signaling.     

Protection from abortion by heme oxygenase-1 up-regulation is associated with increased levels of Bag-1 and neuropilin-1 at the fetal-maternal interface

Tolerance mechanisms allowing pregnancy success resemble those involved in allograft acceptance. Heme oxygenase (HO) is a tissue-protective molecule, which allows graft acceptance and is known to have antiapoptotic effects on several cell types. We previously reported down-regulated levels of HO-1 and HO-2 in placenta from allopregnant mice undergoing abortion. In this study, we analyzed whether the up-regulation of HO-1 by cobalt-protoporphyrin (Co-PP) during implantation window can rescue mice from abortion. Induction of HO-1 by Co-PP treatment prevented fetal rejection, whereas the down-regulation of HOs by zinc-protoporphyrin application boosted abortion. The beneficial effect of HO-1 induction was not related to a local shift to Th2-profile or to a change in the NO system. Interestingly, the expression of the antiapoptotic/cytoprotective molecule Bag-1 as well as the levels of neuropilin-1, a novel marker for T regulatory cells, were up-regulated after Co-PP treatment. Our data strongly support a very important role for HO-1 in fetal allotolerance and suggest that HO-1 might be protective by up-regulating tissue protective molecules, i.e., Bag-1, and by activating T regulatory cells rather than by changing the local cytokine profile.     

Una Polyporacea rara: Trametes ljubarskyi Pilàt,primo ritrovamento in Italia. VII

Abstract

A rare polypore: Trametes ljubarskyi Pilàt, new to Italy. VII. - The presence of Trametes ljubarskyi Pil. (Polyporaceae) is reported for the first time in Italy.     

Aphyllophorales Della Riserva Naturale Integrale di Sasso Fratino (Forlì), Italia

Abstract

The author deals with the results of a research on the presence of Aphyllophorales in Sasso Fratino Forest, an Integral Natural Reserve, inside the Foreste Casentinesi National Park. The research started in 1987 and till now 171 wood-inhabiting species have been collected. Some of them are new to the Italian mycoflora: Antrodiella fissiliformis, Ceriporia alachuana, Laeticorticium meridioroseum, Parvobasidium cretatum, Pycnoporellus fulgens, while some other must be considered very rare species in Italy: Ganoderma carnosum, Lobulicium occultum, Stereum insignitum, Trechispora echynocystis.     

Antrodia onychoides (Egel.) Ryv. specie nuova per l'Italia. II

Abstract

Antrodia onychoides (Egel.) Ryv., new to Italy and very rare species in Europe. II. - The paper is concerned with the first Italian collection of A. onychoides, a resupinate polypore. From the literature, this is the fourth European finding of Antrodia onychoides and follows the first collection, occurred in 1913 near Oslo, in Norway, the second in France and the third in Finland.

Macroscopically A. onychoides could be misdetermined as a Tyromyces however, on the basis of microscopical features, there is no doubt concerning its determination as a species of Antrodia genus.     

Pain in Paget's disease: a retrospective study of treatment efficacy

The authors addressed the role and the management of pain in Paget's disease by a retrospective study. The objectives were: to assess the presence of pain in Paget's disease; to look for a relationship between pain and the levels of total alkaline phosphatase (total ALP); to verify if the most commonly used drugs in Paget's disease, calcitonin and bisphosphonates, were able to reduce the pain and the levels of total ALP. The study analyzed 107 Italian patients with Paget's disease who were hospitalized at the same Institute between 1970 and 2010; all patients affected by severe arthritis were excluded. From the analysis of the clinical records it emerged that as many as 85% of patients had pain and that total ALP was also increased in most of the patients with pain in comparison with patients without pain. The clinical and metabolic effects of different therapies were then assessed: many patients had not received any specific therapy (58%), others had been treated with calcitonin (25%) and others with bisphosphonates (17%). In fact, the patients treated with bisphosphonates had significantly lower levels both of pain and total ALP. The authors hypothesize that the pain in Paget's disease has a primary origin and is correlated to the degree of bone metabolic hyperactivity. Finally, treatment with bisphosphonates appeared to be the most appropriate treatment, having been able to control both the pain and the metabolic hyperactivity.     

Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta

This study tested whether sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 microM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 microM), a sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by approximately 30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only approximately 10%. In contrast, prazosin (1 microM), an alpha-adrenergic receptor antagonist, still completely relaxed the 0.3 muM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by approximately 30%, whereas Ni(2+) and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.     

A phylogenetic analysis of Antrodia s.l. based on nrDNA ITS sequences, with emphasis on rhizomorphic European species

The rhizomorphic European species of Antrodia, belonging to the traditionally called Antrodia radiculosa group, are investigated. On the basis of morphological and molecular analysis, the genus Fibroporia is supported. Specimens from Central Europe previously ascribed to Antrodia radiculosa constitute a species of their own, and are herein described as Fibroporia bohemica. Moreover, a new combination, Fibroporia citrina, is proposed.