Glucose transporter 2 expression is down regulated following P2X7 activation in enterocytes

With the diabetes epidemic affecting the world population, there is an increasing demand for means to regulate glycemia. Dietary glucose is first absorbed by the intestine before entering the blood stream. Thus, the regulation of glucose absorption by intestinal epithelial cells (IECs) could represent a way to regulate glycemia. Among the molecules involved in glycemia homeostasis, extracellular ATP, a paracrine signaling molecule, was reported to induce insulin secretion from pancreatic β cells by activating P2Y and P2X receptors. In rat's jejunum, P2X7 expression was previously immunolocalized to the apex of villi, where it has been suspected to play a role in apoptosis. However, using an antibody recognizing the receptor extracellular domain and thus most of the P2X7 isoforms, we showed that expression of this receptor is apparent in the top two‐thirds of villi. These data suggest a different role for this receptor in IECs. Using the non‐cancerous IEC‐6 cells and differentiated Caco‐2 cells, glucose transport was reduced by more than 30% following P2X7 stimulation. This effect on glucose transport was not due to P2X7‐induced cell apoptosis, but rather was the consequence of glucose transporter 2 (Glut2)'s internalization. The signaling pathway leading to P2X7‐dependent Glut2 internalization involved the calcium‐independent activation of phospholipase Cγ1 (PLCγ1), PKCδ, and PKD1. Although the complete mechanism regulating Glut2 internalization following P2X7 activation is not fully understood, modulation of P2X7 receptor activation could represent an interesting approach to regulate intestinal glucose absorption. J. Cell. Physiol. 228: 120–129, 2013. © 2012 Wiley Periodicals, Inc.     

SDF‐1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception

The precise mechanisms of SDF‐1 (CXCL12) in angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive intussusceptive angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF‐1 and CXCR4. In the current study, we demonstrated SDF‐1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF‐1 expression in wild‐type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF‐1/CXCR4 signalling by AMD3100 perturbs intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF‐1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF‐1 application and two times less after blocking this pathway. Bone marrow‐derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF‐1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF‐1/CXCR4 signalling in intussusceptive angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.     

Characterization and potential antitumor effect of a heteropolysaccharide produced by the red alga Porphyridium sordidum

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all chemotherapy drugs currently on the market cause serious side effects. Fortunately, several studies have shown that some non‐toxic biological macromolecules, including algal polysaccharides, possess anti‐cancer activities or can increase the efficacy of conventional chemotherapy drugs. Polysaccharides are characteristic secondary metabolites of many algae. The efficacy of polysaccharides on the normal and cancer cells is not well investigated, but our investigations proved a cell specific effect of a newly isolated extracellular polysaccharide from the red microalga Porphyridium sordidum. The investigated substance was composed of xylose:glucose and galactose:manose:rhamnose in a molar ratio of 1:0.52:0.44:0.31. Reversible electroporation has been exploited to increase the transport through the plasma membrane into the tested breast cancer tumor cells MCF‐7 and MDA‐MB231. Application of 75 µg/mL polysaccharide in combination with 200 V/cm electroporation induced 40% decrease in viability of MDA‐MB231 cells and changes in cell morphology while control cells (MCF10A) remained with normal morphology and kept vitality.     

High-quality draft genome sequence of Pseudomonas aeruginosa san ai,an environmental isolate resistant to heavy metals

Extremophiles - The strain Pseudomonas aeruginosa san ai, isolated from an extreme environment (industrial mineral cutting oil, pH 10), is able to survive and persist in the presence of a variety...     

Beta-aspartylpeptides as substrates of L-asparaginases from Escherichia coli and Erwinia chrysanthemi

L-Asparaginase is known to catalyze the hydrolysis of L-asparagine to L-aspartic and ammonia, but little is known about its action on peptides. When we incubated L-asparaginases purified either from Escherichia coli or Erwinia chrysanthemi - commonly used as chemotherapeutic agents because of their antitumour activity - with eight small beta-aspartylpeptides such as beta-aspartylserineamide, beta-aspartylalanineamide, beta-aspartylglycineamide and beta-aspartylglycine, we found that both L-asparaginases could catalyze the hydrolysis of five of them yielding L-aspartic acid and amino acids or peptides. Our data show that L-asparaginases can hydrolyze beta-aspartylpeptides and suggest that L-asparaginase therapy may affect the metabolism of beta-aspartylpeptides present in human body.     

Two new sulfated furostanol saponins from Tribulus terrestris

The known furostanol saponins methylprotodioscin and protodioscin and two new sulfated saponins, sodium salt of 26-O-beta-glucopyranosyl-22alpha-methoxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (methylprototribestin) and sodium salt of 26-O-beta-glucopyranosyl-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (prototribestin) have been isolated from the aerial parts of Tribulus terrestris L. growing in Bulgaria. The structures of the new compounds were elucidated on the basis of 1D and 2D (DQF-COSY, TOCSY, HSQC-TOCSY, HSQC, HMBC, ROESY) NMR data, ESI mass spectra and chemical transformation.     

The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation

Immune activation is accompanied by induction of indoleamine (2,3)-dioxygenase (IDO), an enzyme which degrades tryptophan, a phenomenon which plays a role in the pathophysiology of major depression and post-natal depression and anxiety states. TRYCATs - tryptophan catabolites along the IDO pathway - such as kynurenine, kynurenic acid, xanthurenic acid, and quinolinic acid, have multiple effects, e.g. apoptotic, anti- versus pro-oxidant, neurotoxic versus neuroprotective, and anxiolytic versus anxiogenic effects. The aim of the present study was to study the immune effects of the above TRYCATS. Toward this end we examined the effects of the above TRYCATs on the LPS + PHA-induced production of interferon-gamma (IFNgamma), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFalpha) in 18 normal volunteers. We found that the production of IFNgamma was significantly decreased by all 4 catabolites. Xanthurenic acid and quinolinic acid decreased the production of IL-10. Kynurenine, kynurenic acid, and xanthurenic acid, decreased the IFNgamma/IL-10 production ratio, whereas quinolinic acid increased this ratio. Kynurenic acid significantly reduced the stimulated production of TNFalpha. It is concluded that kynurenine, kynurenic acid, and xanthurenic acid have anti-inflammatory effects trough a reduction of IFNgamma, whereas quinolinic acid has pro-inflammatory effects in particular via significant decreases in IL-10. Following inflammation-induced IDO activation, some TRYCATs, i.e. kynurenine, kynurenic acid, and xanthurenic acid, exert a negative feedback control over IFNgamma production thus downregulating the initial inflammation, whereas an excess of quinolinic acid further aggravates the initial inflammation.     

Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression

Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of oxidative and nitrosative stress (O&NS) and an inflammatory response. Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of the present study is to examine whether depression and CFS are characterized by an IgM-mediated immune response directed against Pi. Toward this end, this study examines the serum IgM antibodies directed against Pi in 14 patients with major depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal controls. We found that the prevalence and mean value for the serum IgM levels directed against Pi were significantly greater in patients with major depression and CFS than in normal controls and patients with partial CFS. There were significant and positive correlations between serum IgM levels directed against Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression. The results show that an IgM-related immune response directed against Pi may occur in both depression and CFS and may play a role in the pathophysiology of the key symptom of CFS and major depression. It is suggested that the above disorders in Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies may have biological effects, for example, by changing inositol 1,4,5-triphosphate (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with intracellular signalling processes. Future research in major depression and CFS should focus on the functional consequences of the immune responses directed against Pi.