Promigratory and proangiogenic effects of AdipoRon on bone marrow-derived mesenchymal stem cells: an in vitro study

Objectives

To investigate the effect of AdipoRon on major factors involved in survival, migration and neovascularization of rat bone marrow-derived mesenchymal stem cells.

Results

AdipoRon promoted the MSCs viability. Real-time PCR indicated that the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1) C-X-C chemokine receptor type 4 (CXCR4), C–C chemokine receptor type 2 (CCR2), vascular endothelial growth factor matrix metalloproteinase-2 (MMP-2) and MMP-9 were upregulated in AdipoRon-treated MSCs compared to control groups. Prostaglandin E2 (PGE2) level, as well as migration ability of MSCs (scratch assay) was enhanced by AdipoRon preconditioning.

Conclusion

Preconditioning of MSCs with AdipoRon prior to transplantation could enhance cell survival, angiogenesis and migration via activating the COX-2/PGE2/HIF-1 pathway and other contributing factors.

     

Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus

Vascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits α- and β-catenins and γ-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of α- and β-catenins and γ-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis.     

Engineered rhizosphere: the trophic bias generated by opine-producing plants is independent of the opine type, the soil origin, and the plant species

In a previous study, we demonstrated that transgenic Lotus plants producing opines (which are small amino acid and sugar conjugates) specifically favor growth of opine-degrading rhizobacteria. The opine-induced bias was repeated and demonstrated with another soil type and another plant species (Solanum nigrum). This phenomenon is therefore independent of both soil type and plant species.     

Neuropeptides and amphibian prey-catching behavior

In mammals, a number of hypothalamic neuropeptides have been implicated in stress-induced feeding disorders. Recent studies in anurans suggest that stress-related neuropeptides may act on elemental aspects of visuomotor control to regulate feeding. Corticotropin-releasing hormone (CRH) and alpha-melanocyte-stimulating hormone, potent an orexic peptides in mammals, inhibit visually-guided prey-catching in toads. Neuropeptide Y (NPY), an orexic peptide in mammals, may be an important neuromodulator in inhibitory pre-tectal-tectal pathways involved in distinguishing predator and prey. Melanocortin, NPY and CRH neurons project onto key visuomotor structures within the amphibian brain, suggesting physiological roles in the modulation of prey-catching. Thus, neuropeptides involved in feeding behavior in mammals influence the efficacy of a visual stimulus in releasing prey-catching behavior. These neuropeptides may play an important role in how frogs and toads gather and process visual information, particularly during stress.     

The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of CD4

The genomes of several poxviruses contain open reading frames with homology to the K3 and K5 genes of Kaposi's sarcoma-associated herpesvirus (KSHV) and the K3 gene of murine gammaherpesvirus 68, which target major histocompatibility complex class I (MHC-I) as well as costimulatory molecules for proteasomal or lysosomal degradation. The homologous gene product of myxomavirus (MV), M153R, was recently shown to reduce the cell surface expression of MHC-I. In addition, normal MHC-I surface expression was observed in cells infected with MV lacking M153R (J. L. Guerin, J. Gelfi, S. Boullier, M. Delverdier, F. A. Bellanger, S. Bertagnoli, I. Drexler, G. Sutter, and F. Messud-Petit, J. Virol. 76:2912-2923, 2002). Here, we show that M153R also downregulates the T-cell coreceptor CD4 and we study the molecular mechanism by which M153R achieves the downregulation of CD4 and MHC-I. Upon M153R expression, CD4 was rapidly internalized and degraded in lysosomes, whereas deletion of M153R from the genome of MV restored CD4 expression. The downregulation of both CD4 and MHC-I was dependent on the presence of lysine residues in their cytoplasmic tails. Increased ubiquitination of CD4 was observed upon coexpression with M153R in the presence of inhibitors of lysosomal acidification. Surface expression of CD4 was restored upon overexpression of Hrs, a ubiquitin interaction motif-containing protein that sorts ubiquitinated proteins into endosomes. Moreover, the purified PHD/LAP zinc finger of M153R catalyzed the formation of multiubiquitin adducts in vitro. Our data suggest that M153R acts as a membrane-bound ubiquitin ligase that conjugates ubiquitin to the cytoplasmic domain of substrate glycoproteins, with ubiquitin serving as a lysosomal targeting signal. Since a similar mechanism was recently proposed for KSHV K5, it seems that members of the unrelated families of gamma-2 herpesviruses and poxviruses share a common immune evasion mechanism that targets host cell immune receptors.     

Crystal structure, magnetic and electrochemical properties of five-coordinate copper (II) complexes with 1,10-phenanthroline-5,6-dione

Three new five-coordinate Cu^II complexes, [Cu(tpy)(phen-dione)](PF₆)₂, [Cu(phen)(phen-dione)Cl]PF₆ and [Cu(bpy)(phen-dione)Cl]PF₆ (tpy = 2,2′;6′,2″-terpyridine, phen = 1,10-phenanthroline and phen-dione = 1,10-phenanthroline-5,6-dione) have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopies and cyclic voltammetry.The complex of [Cu(tpy)(phen-dione)](PF₆)₂ crystallized with one molecule of acetonitrile. The ortep drawing of [Cu(tpy)(phen-dione)](PF₆)₂ · CH₃CN shows that the coordination geometry around Cu^II is a distorted trigonal- bipyramid. Due to the steric hindrance of in the unit cell, the tpy ligands in each complex cation cannot interact in a π-π fashion. The effective magnetic moment (μ_eff) of the complexes was measured by the Evans method. The cyclic voltammograms at Pt disk electrode for these complexes display only one reversible Cu(II)/Cu(I) redox couple.     

More Related Gene Pathways to Vincristine-Induced Death Events in a Human T-Acute Lymphoblastic Leukemia Cell Line

Background:Acute lymphoblastic leukemia (ALL) is common in children but rare in adults. Vincristine (VCR) is one of the drugs used at the beginning of treatment. Some genes are resistant to VCR in B-ALL.Methods:Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC₅₀ in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. Total RNA was isolated from the cells and cDNA was prepared. The Human Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells. Protein-protein interaction was analyzed by STRING software.Results:We identified 66 differentially expressed genes as comparison to untreated cells. The response to VCR-induced apoptotic events was remarkable in the pathways of heat shock protein, topoisomerases, protein kinases, cathepsins and cell cycle. In other pathways, there were resistant genes as well as sensitive genes to VCR treatment. Some proteins like HSP90AA1 and ESR1 had determining associations with other proteins.Conclusion:The results suggest VCR target genes in T-ALL cells may be beneficial biomarkers for ALL treatment and can be used to select appropriate synergistic drugs for VCR.Key Words: ALL, Gene expression profile, Jurkat, PCR array, Vincristine