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Chemical Compound Review

AC1LCUYD     4-[2-[2-[3-acetamido-5- hydroxy-2-[hydroxy...

Synonyms: AGN-PC-00IO57
 
 
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Disease relevance of C4

  • Intravenous administration of the concentrate during acute abdominal or laryngeal attacks of hereditary angioedema in five patients resulted in abatement of symptoms in addition to increased serum C4 activity [1].
  • The complexes comprised IgG, IgM, IgA, complement components C3, C4, C5 and IgG antibody against Escherichia coli and Bacillus fragilis [2].
  • The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea [3].
  • To assess the role of complement in renal infection, we studied a model of Escherichia coli-induced pyelonephritis in mice deficient in complement components C3 and C4 [4].
  • This observation provides new insight to a long-standing enigma that the major predisposing factor in lupus is deficiency in complement C1q or C4 [5].
 

Psychiatry related information on C4

  • Complement C4 allotypes in Alzheimer's disease [6].
  • Secondary antihemagglutinin(Sb) antibodies also exhibit the C4 Id although less frequently (10 to 15%) [7].
  • Oral temperature (OT), reaction time (RT) in a visual vigilance task, and electroencephalogram (EEG; C3, C4, T3, and T4) while performing the task were recorded every 2 hours during TSD and after recovery sleep [8].
  • Scalp-recorded direct current (DC) potentials and their topographical distribution (F3, F4, C3, C4 and Pz) were investigated at the transition from wakefulness to sleep, and during NREM-REM sleep and REM-NREM sleep transitions in 11 healthy men during normal sleep [9].
  • 4. The coordinated reciprocal motor activity between the C4 ventral root and IIM changed to a largely overlapping pattern when strychnine (5-10 microM), a glycine receptor antagonist, was added to the perfusate [10].
 

High impact information on C4

  • Most recent evidence suggests that complement also regulates elimination of self-reactive B cells, as breeding of mice that are deficient in C4 or CD21/CD35 with the lupus-prone strain of lpr mice demonstrates an exacerbation of disease due to an increase in autoantibodies [11].
  • Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice [3].
  • GATA-1 is the founding member of a family of DNA-binding proteins that recognize the motif WGATAR through a conserved multifunctional domain consisting of two C4-type zinc fingers [12].
  • The mutant expresses normal levels of prespore-cell transcripts but fails to produce the spore transcript spiA. stkA encodes a predicted 99 kDa protein (STKA) with two putative C4 zinc fingers, one of which is a GATA-type finger, indicating that it may be a transcription factor [13].
  • Such patients have been shown to have low levels of C4 and C2, the natural substrates for C-1, but the levels were not correlated with the presence of symptoms [14].
 

Chemical compound and disease context of C4

  • The early components of human complement (C1, C4, and C2) plus certain serum euglobulins will kill pathogenic strains of Shigella sonnei [15].
  • Guinea pigs deficient in C4 were reconstituted transiently with either human C4A or C4B protein and immunized with the bacteriophage phi X174 [16].
  • Other complement components were normal during remission of lupus, but C1, C4, C2, and C3 levels fell during exacerbations [17].
  • Abnormal skeletal muscle biopsies showed "ragged-red" fibers or congenital fiber type disproportion; serum alanine levels were elevated; in-vivo and in-vitro tests of pyruvate metabolism gave abnormal results; C4 complement was decreased; and the patients' fibroblasts bound immunoglobulin when incubated with autologous serum [18].
  • It is an intermediate in the Krebs and glyoxylate cycles, it is the store for CO2 in C4 and crassulacean acid metabolism plants, it protects plants from aluminum toxicity, it is essential for maintaining the osmotic pressure and charge balance, and it is therefore involved in regulation of stomatal aperture [19].
 

Biological context of C4

  • Following EMS mutagenesis of the C4-bearing chromosome we recovered new lethal L5 alleles, some of which were shown biochemically to have an altered amanitin-resistance polymerase II component [20].
  • The dimorphic chloroplasts of the C4 plant Panicum maximum contain identical genomes [21].
  • We genetically mapped C4 to position 35.66 on the X chromosome and cytogenetically localized it to the polytene chromosome band interval 10C2-10D4 [20].
  • Kranz anatomy is not essential for terrestrial C4 plant photosynthesis [22].
  • A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B [23].
 

Anatomical context of C4

  • This species accomplishes C4 photosynthesis through spatial compartmentation of photosynthetic enzymes, and by separation of two types of chloroplasts and other organelles in distinct positions within the chlorenchyma cell cytoplasm [22].
  • Here we show that expression of a human equivalent to Drosophila's C4 pol II in human cultured cells affects alternative splicing of the fibronectin EDI exon and adenovirus E1a pre-mRNA [24].
  • The immune adherence receptor, the only one of the two shared in common with erythrocytes, was specific for C4 or the C3c region of C3b, but was unreactive with C3d [25].
  • We conclude that the C4 clones represent cells at the earliest stage of T cell development, i.e., Pro-T lymphocytes [26].
  • Short-term cultures of human peripheral blood monocytes were shown to synthesize the alternative pathway complement components C3, factors B (B) and D (D), and properdin, the regulatory proteins C3b inactivator (C3bINA) and beta 1H, in addition to C2, C4, and C5 [27].
 

Associations of C4 with other chemical compounds

  • Here we report that tobacco, a typical C3 plant, shows characteristics of C4 photosynthesis in cells of stems and petioles that surround the xylem and phloem, and that these cells are supplied with carbon for photosynthesis from the vascular system and not from stomata [28].
  • These photosynthetic cells possess high activities of enzymes characteristic of C4 photosynthesis, which allow the decarboxylation of four-carbon organic acids from the xylem and phloem, thus releasing CO2 for photosynthesis [28].
  • The complement system enhances antibody responses to T-dependent antigens, but paradoxically, deficiencies in C1 and C4 are strongly linked to autoantibody production in humans [29].
  • We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein [30].
  • c-kit ligand (KL) activated mouse bone marrow-derived mast cells (BMMC) for the dose- and time-dependent release of arachidonic acid from cell membrane phospholipids, with generation of leukotriene (LT) C4 in preference to prostaglandin (PG)D2 [31].
 

Gene context of C4

  • In the second model, deficiency in CD21/CD35 or C4 combined with CD95 deficiency results in high titers of anti-nuclear antibodies leading to severe lupus-like disease [32].
  • We find that self-reactive B lymphocytes deficient in complement receptors CD21/CD35 or transferred into mice deficient in the complement protein C4 are not anergized by soluble self-antigen [32].
  • Gene conversion is the probable mechanism by which a C4A gene is found at the second C4 locus normally occupied by C4B genes [30].
  • By linkage and association studies in a family material it has been shown that a structural C4 locus is situated in the HLA region of chromosome 6 very close to the HLA-B and Bf loci [33].
  • However, the large size (approximately 30 kb) of the individual CYP21 + C4 repeat units together with the difficulty in identifying reliable CYP21A- and CYP21B-specific markers has prevented direct monitoring of gene organization on individual haplotypes by conventional Southern analyses [34].
 

Analytical, diagnostic and therapeutic context of C4

  • We found that C4- or C3-deficient mice were much more sensitive to caecal ligation and puncture than wild-type (WT) controls (100% versus 20% in 24-h mortality, respectively) [35].
  • These effects may be due in part to the action of leukotrienes D4 and C4, which were identified by bioassay and high-pressure liquid chromatography in the lung effluent after stimulation by platelet-activating factor [36].
  • Synthesis of compounds with properties of leukotrienes C4 and D4 in gerbil brains after ischemia and reperfusion [37].
  • MDF was purified 6,140-fold by a seven-step procedure: extraction with acid-ethanol; precipitation with ether; and fractionation on gel filtration, anion-exchange, diphenyl reversed-phase and C4 reversed-phase HPLC columns, the last column twice [38].
  • The C4 polymorphism in man has been studied by immunofixation electrophoresis, crossed immunoelectrophoresis, and functional detection after agarose gel electrophoresis [33].

References

  1. Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor. Gadek, J.E., Hosea, S.W., Gelfand, J.A., Santaella, M., Wickerhauser, M., Triantaphyllopoulos, D.C., Frank, M.M. N. Engl. J. Med. (1980) [Pubmed]
  2. Arthritis associated with intestinal-bypass procedure for morbid obesity. Complement activation and characterization of circulating cryoproteins. Wands, J.R., LaMont, J.T., Mann, E., Isselbacher, K.J. N. Engl. J. Med. (1976) [Pubmed]
  3. Rnx deficiency results in congenital central hypoventilation. Shirasawa, S., Arata, A., Onimaru, H., Roth, K.A., Brown, G.A., Horning, S., Arata, S., Okumura, K., Sasazuki, T., Korsmeyer, S.J. Nat. Genet. (2000) [Pubmed]
  4. Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli. Springall, T., Sheerin, N.S., Abe, K., Holers, V.M., Wan, H., Sacks, S.H. Nat. Med. (2001) [Pubmed]
  5. The role of complement in B cell activation and tolerance. Carroll, M.C. Adv. Immunol. (2000) [Pubmed]
  6. Complement C4 allotypes in Alzheimer's disease. Nerl, C.W., Mayeux, R., O'Neill, G.J. Lancet (1982) [Pubmed]
  7. V region gene usage and somatic mutation in the primary and secondary responses to influenza virus hemagglutinin. Clarke, S.H., Staudt, L.M., Kavaler, J., Schwartz, D., Gerhard, W.U., Weigert, M.G. J. Immunol. (1990) [Pubmed]
  8. Time course of reaction time and EEG while performing a vigilance task during total sleep deprivation. Corsi-Cabrera, M., Arce, C., Ramos, J., Lorenzo, I., Guevara, M.A. Sleep. (1996) [Pubmed]
  9. Slow potential shifts at sleep--wake transitions and shifts between NREM and REM sleep. Marshall, L., Molle, M., Michaelsen, S., Fehm, H.L., Born, J. Sleep. (1996) [Pubmed]
  10. Intercostal expiratory activity in an in vitro brainstem-spinal cord-rib preparation from the neonatal rat. Iizuka, M. J. Physiol. (Lond.) (1999) [Pubmed]
  11. The role of complement and complement receptors in induction and regulation of immunity. Carroll, M.C. Annu. Rev. Immunol. (1998) [Pubmed]
  12. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nichols, K.E., Crispino, J.D., Poncz, M., White, J.G., Orkin, S.H., Maris, J.M., Weiss, M.J. Nat. Genet. (2000) [Pubmed]
  13. Identification of the cell fate gene stalky in Dictyostelium. Chang, W.T., Newell, P.C., Gross, J.D. Cell (1996) [Pubmed]
  14. Prekallikrein activation and high-molecular-weight kininogen consumption in hereditary angioedema. Schapira, M., Silver, L.D., Scott, C.F., Schmaier, A.H., Prograis, L.J., Curd, J.G., Colman, R.W. N. Engl. J. Med. (1983) [Pubmed]
  15. Complement-mediated bactericidal system: evidence for a new pathway of complement action. Moreau, S.C., Skarnes, R.C. Science (1975) [Pubmed]
  16. Structural differences between the two human complement C4 isotypes affect the humoral immune response. Finco, O., Li, S., Cuccia, M., Rosen, F.S., Carroll, M.C. J. Exp. Med. (1992) [Pubmed]
  17. Hereditary deficiency of the fifth component of complement in man. I. Clinical, immunochemical, and family studies. Rosenfeld, S.I., Kelly, M.E., Leddy, J.P. J. Clin. Invest. (1976) [Pubmed]
  18. Mitral valve prolapse and ophthalmoplegia: a progressive, cardioneurologic syndrome. Darsee, J.R., Miklozek, C.L., Heymsfield, S.B., Hopkins, L.C., Wenger, N.K. Ann. Intern. Med. (1980) [Pubmed]
  19. The plant homolog to the human sodium/dicarboxylic cotransporter is the vacuolar malate carrier. Emmerlich, V., Linka, N., Reinhold, T., Hurth, M.A., Traub, M., Martinoia, E., Neuhaus, H.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. Genetic and biochemical characterization of mutants at an RNA polymerase II locus in D. melanogaster. Greenleaf, A.L., Weeks, J.R., Voelker, R.A., Ohnishi, S., Dickson, B. Cell (1980) [Pubmed]
  21. The dimorphic chloroplasts of the C4 plant Panicum maximum contain identical genomes. Walbot, V. Cell (1977) [Pubmed]
  22. Kranz anatomy is not essential for terrestrial C4 plant photosynthesis. Voznesenskaya, E.V., Franceschi, V.R., Kiirats, O., Freitag, H., Edwards, G.E. Nature (2001) [Pubmed]
  23. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Carroll, M.C., Campbell, R.D., Bentley, D.R., Porter, R.R. Nature (1984) [Pubmed]
  24. A slow RNA polymerase II affects alternative splicing in vivo. de la Mata, M., Alonso, C.R., Kadener, S., Fededa, J.P., Blaustein, M., Pelisch, F., Cramer, P., Bentley, D., Kornblihtt, A.R. Mol. Cell (2003) [Pubmed]
  25. Specificity of human lymphocyte complement receptors. Ross, G.D., Polley, M.J. J. Exp. Med. (1975) [Pubmed]
  26. Molecular, cellular, and functional properties of bone marrow T lymphocyte progenitor clones. Palacios, R., Kiefer, M., Brockhaus, M., Karjalainen, K., Dembić, Z., Kisielow, P., von Boehmer, H. J. Exp. Med. (1987) [Pubmed]
  27. Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. Whaley, K. J. Exp. Med. (1980) [Pubmed]
  28. Characteristics of C4 photosynthesis in stems and petioles of C3 flowering plants. Hibberd, J.M., Quick, W.P. Nature (2002) [Pubmed]
  29. Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. Chen, Z., Koralov, S.B., Kelsoe, G. J. Exp. Med. (2000) [Pubmed]
  30. Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus. Braun, L., Schneider, P.M., Giles, C.M., Bertrams, J., Rittner, C. J. Exp. Med. (1990) [Pubmed]
  31. The immediate phase of c-kit ligand stimulation of mouse bone marrow-derived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2 and 5-lipoxygenase. Murakami, M., Austen, K.F., Arm, J.P. J. Exp. Med. (1995) [Pubmed]
  32. A critical role for complement in maintenance of self-tolerance. Prodeus, A.P., Goerg, S., Shen, L.M., Pozdnyakova, O.O., Chu, L., Alicot, E.M., Goodnow, C.C., Carroll, M.C. Immunity (1998) [Pubmed]
  33. The genetic polymorphism of the fourth component of human complement: methodological aspects and a presentation of linkage and association data relevant to its localization in the HLA region. Teisberg, P., Olaisen, B., Jonassen, R., Gedde-Dahl, T., Thorsby, E. J. Exp. Med. (1977) [Pubmed]
  34. Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes. Collier, S., Sinnott, P.J., Dyer, P.A., Price, D.A., Harris, R., Strachan, T. EMBO J. (1989) [Pubmed]
  35. Impaired mast cell-dependent natural immunity in complement C3-deficient mice. Prodeus, A.P., Zhou, X., Maurer, M., Galli, S.J., Carroll, M.C. Nature (1997) [Pubmed]
  36. Nonimmunological production of leukotrienes induced by platelet-activating factor. Voelkel, N.F., Worthen, S., Reeves, J.T., Henson, P.M., Murphy, R.C. Science (1982) [Pubmed]
  37. Synthesis of compounds with properties of leukotrienes C4 and D4 in gerbil brains after ischemia and reperfusion. Moskowitz, M.A., Kiwak, K.J., Hekimian, K., Levine, L. Science (1984) [Pubmed]
  38. Purification of macrophage deactivating factor. Srimal, S., Nathan, C. J. Exp. Med. (1990) [Pubmed]
 
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