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C3 Protein (c3 + protein)
Selected AbstractsInhibition of Rho-dependent pathways by Clostridium botulinum C3 protein induces a proinflammatory profile in microgliaGLIA, Issue 11 2008Anja Hoffmann Abstract Successful regeneration in the central nervous system crucially depends on the adequate environment. Microglia as brain immune-competent cells importantly contribute to this task by producing pro- and anti-inflammatory mediators. Any environmental change transforms these cells towards an activated phenotype, leading to major morphological, transcriptional and functional alterations. Rho GTPases affect multiple cellular properties, including the cytoskeleton, and C3 proteins are widely used to study their involvement. Especially C3bot from Clostridium botulinum has been considered to promote neuronal regeneration by changing Rho activity. Yet C3bot may exert cellular influences through alternative mechanisms. To determine the role of Rho-dependent pathways in microglia we investigated the influence of C3bot on functional properties of cultivated primary mouse microglial cells. Nanomolar concentrations of C3bot transformed microglia towards an activated phenotype and triggered the release of nitric oxide and several proinflammatory cyto- and chemokines. These inductions were not mediated by the ROCK-kinase pathway, since its selective inhibitors Y27632 and H1152 had no effect. C3-induced and Rho-mediated NO release was instead found to be under the control of NF,B, as revealed by treatment with the NF,B inhibitor PDTC. Thus, C3bot induces a proinflammatory response in microglia resembling the classical proinflammatory phenotype elicited by bacterial LPS. The findings are relevant for the use of C3bot in regenerative approaches. © 2008 Wiley-Liss, Inc. [source] Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2006J. Ren Abstract Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation. J. Med. Virol. 78:551,560, 2006. © 2006 Wiley-Liss, Inc. [source] Complement 3 deficiency impairs early pregnancy in miceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2009Wang-Ngai Chow Human oviductal cells produce complement-3 (C3) and its derivative, iC3b. These molecules are important in immune responses. Our recent study suggested that iC3b also possessed embryotrophic activity and it stimulates the blastulation and hatching rates of in vitro cultured mouse embryos. The objective is to study the impact of C3 deficiency on early pregnancy in vivo using homozygous C3-deficient (C3KO) and wild-type (C3WT) mice. C3 protein was undetectable in the reproductive tissues of C3KO mice. Deficiency in C3 is associated with significantly longer estrous cycle (P,=,0.037). No significant difference was found in the ovulation rate, total cell count in blastocysts and implantation rate between the wild-type and the C3KO mice, though C3KO mice tended to have lower values in the latter two parameters. On day 15 of pregnancy, C3KO mice had fewer conceptus (P,<,0.001) and higher resorption rate (P,<,0.001) than that of C3WT mice. The fetal and placental weights (P,<,0.001) were lower in the C3KO mice. The placenta of C3KO mice had smaller spongiotrophoblast (P,=,0.001) and labyrinth (P,=,0.037). Deficiency in C3 is associated with mild impairment in early pregnancy including longer estrous cycle and higher resorption rates after implantation. The impairment may be related to compromised placental development leading to under-developed fetuses. Mol. Reprod. Dev. 76: 647,655, 2009. © 2009 Wiley-Liss, Inc. [source] Phosphoenolpyruvate carboxylase genes in C3, crassulacean acid metabolism (CAM) and C3/CAM intermediate species of the genus Clusia: rapid reversible C3/CAM switches are based on the C3 housekeeping genePLANT CELL & ENVIRONMENT, Issue 12 2006ANJA VAASEN ABSTRACT The genus Clusia includes species that exhibit either the C3 or crassulacean acid metabolism (CAM) mode of photosynthesis, or those that are able to switch between both modes according to water availability. In order to screen for species-specific genetic variability, we investigated the key carboxylase for CAM, phosphoenolpyruvate carboxylase (PEPC). Sequence analysis of DNA isolated from the obligate CAM species, Clusia hilariana, the obligate C3 species, Clusia multiflora, and an intermediate species that can switch between C3 and CAM photosynthesis, Clusia minor, revealed three different isoforms for C. hilariana and one each for the other two species. Sequence alignments indicated that PEPC from the intermediate species had high homology with the C3 protein and with one of CAM plant proteins. These were assumed to constitute ,housekeeping' proteins, which can also support CAM in intermediate species. The other two isoforms of the CAM plant C. hilariana were either CAM-specific or showed homologies with PEPC from roots. Phylogenetic trees derived from neighbour-joining analysis of amino acid sequences from 13 different Clusia species resulted in two distinct groups of plants with either ,housekeeping' PEPC only, or additionally CAM-related isoforms. Only C. hilariana showed the third, probably root-specific isoform. The high homology of the PEPC from the intermediate species with the C3 protein indicates that for the reversible transition from the C3 to CAM mode of photosynthesis, the C3 type of PEPC is sufficient. Its expression, however, is strongly increased under CAM-inducing conditions. The use of the C3 isoform could have facilitated the evolution of CAM within the genus, which occurred independently for several times. [source] Inhibition of Rho-dependent pathways by Clostridium botulinum C3 protein induces a proinflammatory profile in microgliaGLIA, Issue 11 2008Anja Hoffmann Abstract Successful regeneration in the central nervous system crucially depends on the adequate environment. Microglia as brain immune-competent cells importantly contribute to this task by producing pro- and anti-inflammatory mediators. Any environmental change transforms these cells towards an activated phenotype, leading to major morphological, transcriptional and functional alterations. Rho GTPases affect multiple cellular properties, including the cytoskeleton, and C3 proteins are widely used to study their involvement. Especially C3bot from Clostridium botulinum has been considered to promote neuronal regeneration by changing Rho activity. Yet C3bot may exert cellular influences through alternative mechanisms. To determine the role of Rho-dependent pathways in microglia we investigated the influence of C3bot on functional properties of cultivated primary mouse microglial cells. Nanomolar concentrations of C3bot transformed microglia towards an activated phenotype and triggered the release of nitric oxide and several proinflammatory cyto- and chemokines. These inductions were not mediated by the ROCK-kinase pathway, since its selective inhibitors Y27632 and H1152 had no effect. C3-induced and Rho-mediated NO release was instead found to be under the control of NF,B, as revealed by treatment with the NF,B inhibitor PDTC. Thus, C3bot induces a proinflammatory response in microglia resembling the classical proinflammatory phenotype elicited by bacterial LPS. The findings are relevant for the use of C3bot in regenerative approaches. © 2008 Wiley-Liss, Inc. [source] | ||||||||||