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Gene Review

Gc  -  group specific component

Rattus norvegicus

Synonyms: DBP, DBP02, Dbp, Gc-globulin, Group-specific component, ...
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Disease relevance of Gc

  • In the current study, a cDNA to rat DBP mRNA was cloned from a bacteriophage lambda gt 11 rat liver expression library [1].
  • Alterations in plasma levels and complexing of Gc (vitamin D-binding protein) in rats with endotoxic shock [2].
  • Since complexing with G-actin displaces fatty acids, possible alterations in plasma levels of Gc and extent of complexing were sought in serial samples obtained from rats with shock induced by Salmonella enteritidis endotoxin (12.5-15 mg kg-1) [2].
  • NGF treatment prevented the withdrawal-associated loss, and induced hypertrophy, of cholinergic neurons.These findings show that exogenous NGF protects the phenotype and prevents the withdrawal-induced degeneration of cholinergic neurons in the MS/VDB [3].

Psychiatry related information on Gc

  • These experiments suggest that excitotoxic lesions of the septum/VDB produce deficits in conditional discrimination learning and performance, and that the integrity of the projection to the cingulate cortex is more crucial than that to the hippocampus in this effect [4].
  • Neither lesion affected simple visual or spatial discrimination or reversal learning, also carried out in operant chambers, but both significantly impaired the acquisition and retention of a spatial navigation task (Morris water maze), with the septal/VDB lesions again producing greater deficits than the hippocampal lesions [5].
  • These results indicate state-specific effects on transcription and subsequent protein expression in cell populations associated with behavioral state and further show that the HDB, VDB and VLPO are good candidates for the further study of intracellular events associated with sleep and wakefulness [6].
  • Following AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) lesions of the vertical limb diagonal band of Broca (VDB) which provides the main cholinergic projection to cingulate cortex, animals were not significantly impaired on the 5-choice serial reaction time task [7].
  • Burst firing neurons of the medial septal area (MS/VDB) are thought to pace the HPC theta rhythm during REM sleep and ambulation [8].

High impact information on Gc

  • We report here that NGF treatment significantly reduces both the total neuronal and cholinergic neuronal death found 2 weeks after fimbria fornix transection; there was a sparing of 50% of the neurons in the MS and essentially 100% of those in the VDB that otherwise would have died [9].
  • In experiments 1-3, excitotoxic lesions were made of the septum and VDB in rats using quisqualic acid, which resulted in significant reductions in ChAT activity in the hippocampus and cingulate cortex, but with no effects on cortical monoamines [4].
  • Four experiments examined the role of the cholinergic projections from the septum and vertical limb nucleus of the diagonal band of Broca (VDB) in acquisition and performance of a conditional visual discrimination [4].
  • By transient transfection analysis, we identified three regions in the 5'-flanking region of the rat DBP gene, segments F-2, B, and A, that contain tissue-specific transcriptional determinants [10].
  • These results suggested that the net expression of the DBP gene reflected a balance between the two major HNF1 species; the relative abundance of HNF1alpha and HNF1beta proteins in a cell may thus play a critical role in determining the pattern of gene expression [10].

Chemical compound and disease context of Gc

  • Correlation of these results with glucose, transaminases, and immunoreactive TXB2 and 6-keto-PGF1 alpha indicated that decreased absolute levels of Gc represent a consistent early change in endotoxic shock and that the percentage of Gc complexed is an accurate prognostic indicator of severity [2].

Biological context of Gc


Anatomical context of Gc


Associations of Gc with chemical compounds

  • The encoded DBP contains a characteristic placement of cysteine residues, identical to that in albumin, suggesting a similar secondary folding structure [1].
  • Cellular Gc was also phosphorylated in intact cells following treatment with carbachol as a physiological stimulus [15].
  • Recently, a new extracellular pool of unsaturated fatty acids including arachidonate has been found in relation to group-specific component (Gc), a vitamin D-binding plasma protein that sequesters monomeric G-actin [2].
  • Determination of genotypes was performed by coat color and polyacrylamide gel electrophoresis (PAGE of serum protein for the Gc and albumin genes [16].
  • We have found that in ethanol-fed rats there was a significant reduction in the total number of Nissl-stained and cholinergic neurons in the MS/VDB, and that the suppression of ethanol intake further decreased neuron numbers [3].

Other interactions of Gc


Analytical, diagnostic and therapeutic context of Gc

  • Using Northern blot analysis of RNA from multiple rat tissues, the DBP transcripts were present in the expected high levels in the adult liver [12].
  • Unexpectedly, at 32 cycles of PCR, DBP, alpha FP, and ALB mRNAs could be detected at very low levels in all tissues examined [12].
  • This DBP cDNA clone was identified by immunoblotting and its identity was confirmed by immunoprecipitation of a 54-kDa protein after hybrid-assisted translation [1].
  • Actin affinity chromatography in the purification of human, avian and other mammalian plasma proteins binding vitamin D and its metabolites (Gc globulins) [19].
  • This simple, direct-staining technique appears to be suitable for identifying DBP/Gc phenotypes in human populations as well as for semiquantitatively monitoring the plasma actin-scavenger system in vivo in animal models or in human diseases [20].


  1. Rat vitamin D binding protein. Determination of the full-length primary structure from cloned cDNA. Cooke, N.E. J. Biol. Chem. (1986) [Pubmed]
  2. Alterations in plasma levels and complexing of Gc (vitamin D-binding protein) in rats with endotoxic shock. Watt, G.H., Ashton, S.H., Cook, J.A., Wise, W.C., Halushka, P.V., Galbraith, R.M. Circ. Shock (1989) [Pubmed]
  3. Nerve growth factor prevents cell death and induces hypertrophy of basal forebrain cholinergic neurons in rats withdrawn from prolonged ethanol intake. Cadete-Leite, A., Pereira, P.A., Madeira, M.D., Paula-Barbosa, M.M. Neuroscience (2003) [Pubmed]
  4. Effects of excitotoxic lesions of the septum and vertical limb nucleus of the diagonal band of Broca on conditional visual discrimination: relationship between performance and choline acetyltransferase activity in the cingulate cortex. Marston, H.M., West, H.L., Wilkinson, L.S., Everitt, B.J., Robbins, T.W. J. Neurosci. (1994) [Pubmed]
  5. Comparative effects of excitotoxic lesions of the hippocampus and septum/diagonal band on conditional visual discrimination and spatial learning. Marston, H.M., Everitt, B.J., Robbins, T.W. Neuropsychologia. (1993) [Pubmed]
  6. c-Fos expression in the cholinergic basal forebrain after enforced wakefulness and recovery sleep. Greco, M.A., Lu, J., Wagner, D., Shiromani, P.J. Neuroreport (2000) [Pubmed]
  7. Dissociable effects of AMPA-induced lesions of the vertical limb diagonal band of Broca on performance of the 5-choice serial reaction time task and on acquisition of a conditional visual discrimination. Muir, J.L., Bussey, T.J., Everitt, B.J., Robbins, T.W. Behav. Brain Res. (1996) [Pubmed]
  8. Innate differences in medial septal area burst firing neurons and the hippocampal theta rhythm during ambulation in selectively bred rat lines. Breen, T.E., Morzorati, S.L. Brain Res. (1996) [Pubmed]
  9. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Williams, L.R., Varon, S., Peterson, G.M., Wictorin, K., Fischer, W., Bjorklund, A., Gage, F.H. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  10. Vitamin D-binding protein gene transcription is regulated by the relative abundance of hepatocyte nuclear factors 1alpha and 1beta. Song, Y.H., Ray, K., Liebhaber, S.A., Cooke, N.E. J. Biol. Chem. (1998) [Pubmed]
  11. The amino acid sequence of the NH2-terminal portion of rat and human vitamin D binding protein: evidence for a high degree of homology between rat and human vitamin D binding protein. Litwiller, R., Fass, D., Kumar, R. Life Sci. (1986) [Pubmed]
  12. The vitamin D-binding protein, alpha-fetoprotein, albumin multigene family: detection of transcripts in multiple tissues. McLeod, J.F., Cooke, N.E. J. Biol. Chem. (1989) [Pubmed]
  13. NOS induction by NGF in basal forebrain cholinergic neurones: evidence for regulation of brain NOS by a neurotrophin. Holtzman, D.M., Kilbridge, J., Bredt, D.S., Black, S.M., Li, Y., Clary, D.O., Reichardt, L.F., Mobley, W.C. Neurobiol. Dis. (1994) [Pubmed]
  14. Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats. Vale-Martínez, A., Baxter, M.G., Eichenbaum, H. Eur. J. Neurosci. (2002) [Pubmed]
  15. Identification of a major endogenous substrate for phospholipid/Ca2+-dependent kinase in pancreatic acini as Gc (vitamin D-binding protein). Wooten, M.W., Nel, A.E., Goldschmidt-Clermont, P.J., Galbraith, R.M., Wrenn, R.W. FEBS Lett. (1985) [Pubmed]
  16. Mapping of the hooded, Gc protein, and albumin gene loci in linkage group VI of the laboratory rat. Shumiya, S., Nagase, S. Biochem. Genet. (1988) [Pubmed]
  17. Proteins of rat serum V: adjuvant arthritis and its modulation by nonsteroidal anti-inflammatory drugs. Ebrini, I., Agnello, D., Miller, I., Villa, P., Fratelli, M., Ghezzi, P., Gemeiner, M., Chan, J., Aebersold, R., Gianazza, E. Electrophoresis (2000) [Pubmed]
  18. Detection of the changes in protein distribution of rat plasma induced by carbon tetrachloride administration by means of two-dimensional electrophoresis. Manabe, T., Okuyama, T., Suzuki, A., Shigematsu, A. J. Chromatogr. (1981) [Pubmed]
  19. Actin affinity chromatography in the purification of human, avian and other mammalian plasma proteins binding vitamin D and its metabolites (Gc globulins). Haddad, J.G., Kowalski, M.A., Sanger, J.W. Biochem. J. (1984) [Pubmed]
  20. Electrophoretic mobility shift assay identifies vitamin D binding protein (Gc-globulin) in human, rat, and mouse sera. Tang, W.X., Bazaraa, H.M., Magiera, H., Cooke, N.E., Haddad, J.G. Anal. Biochem. (1996) [Pubmed]
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