Disease relevance of C3

• Before and during the development of parasitemia, red cells become Coombs-positive for C3, but not for IgG [1].
• Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus [2].
• Intraglomerular C3 synthesis in rats with passive Heymann nephritis [3].
• However, there is little clear information on the role of local C3 synthesis in the pathogenesis of nephritides such as PHN [3].
• Our results suggest that renal cells synthesize C3 mRNA in PHN in a site-specific manner and that locally produced C3 is associated with the development of proteinuria in this model [3].

High impact information on C3

• In the rat there are two non-allelic genes C3(1) and C3(2) for the C3 polypeptide of prostatic steroid binding protein [4].
• Rat prostatic steroid binding protein: DNA sequence and transcript maps of the two C3 genes [4].
• Transcript mapping has shown that there are two distinct C3 transcripts which share a unique 3' terminus but have 5' termini 38 bases apart each preceded by a 'TATA' box homology [4].
• Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2 [5].
• C3 consumption in rat plasma anticoagulated with acid citrate dextrose solution was variable; addition of Mg2+ (5 mM) to plasma anticoagulated with acid citrate dextrose solution augmented C3 consumption [6].

Chemical compound and disease context of C3

• Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways [2].
• Protein tyrosine phosphorylation and invasion by MM1 cells induced by LPA are largely regulated by rho p21, because both were inhibited by Clostridium botulinum C3 exo-enzyme, which is known to specifically inactivate rho p21 [7].
• Tamoxifen exerts agonistic effects on clusterin and complement C3 gene expression in RUCA-I primary xenografts and metastases but not normal uterus [8].
• Therefore, we tested the hypothesis that in neonatal rats subjected to a unilateral HI cerebral insult, prior administration of E. coli lipopolysaccharide (LPS) augments (1) complement-mediated serum hemolytic activity, and (2) C3 mRNA and C9 mRNA levels in hepatic and cerebral tissue [9].

Biological context of C3

• Nucleotide and deduced amino acid sequence of rat complement C3 [10].
• The analysis of the human complement C3 gene reveals the presence of functional FXR response elements in the proximal promoter of C3 [11].
• We conclude that post-ischemic injury led to transient up-regulation of glomerular expression of C3 mRNA [12].
• We therefore investigated the local gene expression of complement component C3, pivotal to complement activation pathways and a mediator of inflammatory injury, in a rat renal transplant model [12].
• In vitro, the dendrimeric form of C3, termed C3d, disrupts NCAM-mediated cell adhesion, induces neurite outgrowth, and triggers intracellular signaling cascades similar to those activated by homophilic NCAM binding [13].

Anatomical context of C3

• Immunohistochemical studies demonstrated the presence of C3 only in the epithelial cells of estrogen-stimulated rat uteri [14].
• To further examine the possibility that the estradiol-regulated secretory protein was C3, an aliquot of radiolabeled media protein from control and estradiol-stimulated rat uteri was incubated with goat anti-rat C3 antibody [14].
• C3 activity in plasmas from normal and tumor-bearing rats was reduced (consumed) during absorption under appropriate conditions with Sepharose 4B, inactivated CNBr Sepharose, or Protein A-Sepharose [6].
• During the early stages of PHN, C3 mRNA expression was detected in mesangial cells and glomerular epithelial cells, whereas such expression was limited to mesangial cells during the late stages of the disease [3].
• In L6 muscle cells, dexamethasone stimulates proteolysis and increases the amount of the proteasome C3 subunit protein by augmenting its transcription [15].

Associations of C3 with chemical compounds

• Estrogen regulation of tissue-specific expression of complement C3 [14].
• In the ventral prostate, these sites change from being completely methylated around the C1, C2, and one of two C3 genes in 10-day-old animals to being unmethylated in 28-day-old animals [16].
• Androgen-dependent enhancement of transcription was assayed by cotransfection of CV1 cells with a rat AR expression vector, pCMVrAR, and C3 genomic fragments or synthetic elements cloned into the reporter vector ptkCAT [17].
• LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60% [2].
• In support of the concept that B. rodhaini organisms contain C3b receptors, we have shown in vitro that parasites will activate the alternate complement pathway, resulting in uptake of radiolabeled C3, and that this uptake is blocked in the presence of trypan blue [1].

Physical interactions of C3

• Androgens transcriptionally regulate the expression of cystatin-related protein and the C3 component of prostatic binding protein in rat ventral prostate and lacrimal gland [18].
• This suggests that dbcAMP-induced synthesis of IL-1beta mediates the C3 production by SchC in an autocrine/paracrine fashion by binding to a functional IL-1 receptor expressed on the surface of SchC [19].
• SVS II binding to SVS IV-7S DNA was greater than its binding to either a comparable fragment of the C3 gene or linearized pUC-19 plasmid, and it was not eliminated by a 100-fold competition [20].

Regulatory relationships of C3

• On the other hand, injection of C3 enzyme did not affect increase in cytoplasmic Ca2+ levels induced by ET-3 [21].
• The cytokine stimulation of AGP and C3 genes is further enhanced by hepatocyte growth factor [22].
• Induction of C3 mRNA and protein by dbcAMP at 24 hours was inhibited >85% by a neutralizing anti-IL-1beta antibody and 76% with an IL-1 receptor antagonist [19].
• Densitometry scans of Northern blots indicated that vinclozolin, p,p'-DDE, and flutamide each induced TRPM-2 mRNA and repressed C3 mRNA compared to vehicle-treated T-implanted controls [23].
• In addition, we have demonstrated by a nuclear run-on assay that Prl significantly enhances the transcription rate of the C3 gene in the rat prostate [24].

Other interactions of C3

• The LE-1 cDNA sequence was homologous with the 3' portion of the C3 mRNA containing the alpha subunit (115 kDa) [14].
• We have recently identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides [25].
• Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1, induction of neurites by the C3 peptide was abrogated [25].
• Although DAI and BPA were very weak stimulators of uterine growth, these substances were able to alter the expression of AR, ER and C3 very strongly [26].
• TNF-alpha alone did not induce C3 expression in SchC [19].

Analytical, diagnostic and therapeutic context of C3

• By reverse transcriptase-polymerase chain reaction, the expression of C3 mRNA increased in two phases [12].
• At 10 minutes, strong linear binding of con A, rabbit IgG, and rat C3 to the endothelium was detected by immunofluorescence in both GC and PC [27].
• In the present study, using nonradioactive in situ hybridization and semiquantitative reverse transcriptase polymerase chain reaction, we examined C3 synthesis in the kidney and its contribution to tissue injury in a rat model of PHN induced by the injection of polyclonal anti-gp330 antibody [3].
• The alteration in the metabolism of C3 in the face of nonparallel changes in IgG metabolism suggests that abnormal glomerular filtration and increased vasopermeability cannot explain the findings [28].
• In situ localization of C3 synthesis in experimental acute renal allograft rejection [12].

References