Disease relevance of C4a

• Using a subtraction cloning strategy, we identified a rat isoform of the complement C4 protein gene whose expression was strongly induced in stellate cells after iron overload [1].
• This study investigated the contribution of local complement synthesis by studying gene expression of the classical pathway component C4 in relation to the site of the tissue injury and the development of proteinuria induced by the pathogenic antibody (sheep anti-GP330) [2].
• Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis [2].
• The dependence on human papillomavirus (HPV) oncoproteins of the growth of cervical cancer cell lines [C4-1, HeLa (both containing HPV 18 DNA), CaSki and SiHa (both containing HPV 16 DNA)], HPV 16-transformed human embryonic kidney cells, and HPV 16-transformed rat brain and 3Y1 cells was examined by using antisense RNA approaches [3].
• Since implication of the C has been demonstrated during neurodegeneration and Wallerian degeneration, without being clearly explained, we investigated the expression of C4 and clusterin mRNA, at the lesion site, after rat sciatic nerve crush injury [4].

High impact information on C4a

• Quantitative mRNA expression analyses revealed that both C4 genes are transcribed in various organs and tissues, but displaying ample differences of C4-1 and C4-2 expression [5].
• The demonstration, with phenylalanine hydroxylase, that one atom of molecular oxygen remains attached to position 5 of pyrimidine cofactor, provides the first strong evidence for activation of oxygen by aromatic amino acid monooxygenases via covalent addition to C4a of tetrahydrobiopterin [6].
• The total cortical C4 mRNA expression assessed by semiquantitative polymerase chain reaction (PCR) increased in a time-dependent manner (P < 0.05), coincident with the onset and progression of proteinuria, and peaking 11 to 14 days after the induction of the disease [2].
• The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a [7].
• The pterin ring of 7-BH(4) shows proper stacking with Phe300, but the distance between the C4a and the active site iron is 0.6 A longer than for bound BH(4), a finding that may be related to the high degree of uncoupling observed for 7-BH(4) [8].

Biological context of C4a

• The distance between C4a in the pteridines and the active site iron was 4.2 +/- 0.5 A for the ensemble of docked conformers [8].

Anatomical context of C4a

• Rat C4a is weakly active in contracting guinea pig ileum at 0.1-1 microM, which is comparable with the activity of human C4a [9].
• In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia [10].
• Expression of clusterin and C4 mRNA during rat peripheral nerve regeneration [4].

Analytical, diagnostic and therapeutic context of C4a

• Results from Ouchterlony and radioimmunoassay analysis indicated that neither rat C5A nor C3a contaminated the C4a preparation [9].
• This study, using in situ hybridization, found that C4 mRNA expression was increased in the glomerular epithelium and the proximal renal tubular epithelium in a distribution similar to that of the targeted GP330 antigen [2].
• Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia [10].

References