Skip to main content
SpringerLink
Log in

Isolation of GIF from porcine brain and studies of its zinc transfer kinetics with apo-carbonic anhydrase

  • Published:
Biometals Aims and scope Submit manuscript

Abstract

Neuronal growth inhibitory factor (GIF) of porcine brain, was isolated and purified by a similar procedure which was used on the isolation of human and bovine GIF. The native porcine protein with stoichiometry of 4Cu+, 3Zn2+ was obtained for the first time. The kinetics of zinc transfer from Cu4Zn3MT-3 to apo-carbonic anhydrase were studied, and zinc transfer rate constants and thermodynamic parameters were obtained. It is found that like other MTs, porcine Cu4Zn3MT-3 can also transfer its zinc atom to apoCA, even much easier than other MTs. A possible association mechanism has been proposed, the formation of Cu4Zn3MT3-apoCA complex may be the rate-determining step. The obtained data indicate besides its neuronal growth inhibitory function, GIF might play a role in cellular Zn homeostasis in brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Armstrong MJ, Meyers DV, Verpoorte JA et al. 1966 Purification and properties of human erythrocyte carbonic anhydrase. J Biol Chem 241, 5137-5149.

    Google Scholar 

  • Bogumil R, Faller P, Pountney DL et al. 1996 Evidence for Cu (I) clusters and Zn (II) clusters in neuronal growth inhibitory factor isolated from bovine brain. Eur J Biochem 238, 698-705.

    Google Scholar 

  • Bogumil R, Faller P, Bina PA et al. 1998 Structural characterization of Cu (I) and Zn (II) sites in neuronal-growth-inhibitory factor by extended X-ray absorption fine structure (EXAFS). Eur J Biochem 255, 172-177.

    Google Scholar 

  • Bongers J, Walton CD, Bell JU et al. 1988 Micromolar protein concentrations and metalloptorein stoichiometries obtained by inductively coupled plasma atomic emission spectrometric determination of sulfur. Analy Chem 60, 2683-2686.

    Google Scholar 

  • Buhler RHO, Kägi JHR. 1979 Metallothionein. In Kägi JHR, Nordberg M, eds. Bäsel: Birkhauser, 211-220.

    Google Scholar 

  • Chen C-F, Wang S-H, Lin L-Y. 1996. Identification and characterization of metallothionein III (Growth Inhibitory Factor) from porcine brain. Comp Biochem Physiol 115B, 27-32.

    Google Scholar 

  • Comeau RD. McDonal KW., Toiman GL et al. 1992 Gram scale purification and preparation of rabbit liver zinc metallothionein. Prep Biochem 22, 151-159.

    Google Scholar 

  • Faller P, Vašák M. 1997 Distinct metal-thiolate clusters in the N-terminal domain of neuronal growth inhibitory factor. Biochemistry 36, 13341-13348.

    Google Scholar 

  • Faller P, Hasler DW, Zerbe O et al. 1999 Evidence for a dynamic structure of human neuronal growth inhibitory factor and for major rearrangements of its metal-thiolate clusters. Biochemistry 38, 10158-10167.

    Google Scholar 

  • Hasler DW, Faller P, Vašák M. 1998 Metal-thiolate clusters in the C-terminal domain of human neuronal growth inhibitory factor (GIF) Biochemistry 37, 14966-14973.

    Google Scholar 

  • Kägi JHR, Schäffer A. 1998 Biochemistry of metallothionein. Biochemistry 27, 8509-8515.

    Google Scholar 

  • Kobayashi H, Uchida Y, Ihara Y et al. 1993 Expression of growth inhibitory factor (GIF) gene in Alzheimer's disease brain. Mol Brain Res 19, 188-194.

    Google Scholar 

  • Li T-Y, Keaker AJ, ShowIII CF et al. 1980 Ligand substitution reactions of metallothioneins with EDTA and apo-carbonic anhydrase. 77, 6334-6338.

  • Margoshes M. Vallee BL. 1957 A cadmium protein from equine kidney cortex. J Am Chem Soc 79, 4813-4814.

    Google Scholar 

  • Nielson KB, Winge DR. 1983 Order of metal binding in metallothionein. J Biol Chem 258, 13063-13069.

    Google Scholar 

  • Öz G, Zangger K. Armitage IM. 2001 Tree-dimensional structure and dynamics of a brain specific growth inhibitory factor: Metallothionein-3. Biochemistry 40, 11433-11441.

    Google Scholar 

  • Pountney DL, Fundel SM, Faller P et al. 1994 Isolation, primary structures and metal binding properties of neuronal growth inhibitory factor (GIF) from bovine and equine brain. FEBS Lett. 345, 193-197.

    Google Scholar 

  • Sadhu C, Gedamu L. 1989 Metal-specific posttranscriptional control of human metallothionein genes. Mol Cell Biol 9, 5738-5741.

    Google Scholar 

  • Stillman MJ, Cai WH, Zelazowski AJ. 1987 Cadmium binding to metallothioneins. Domain specificity in reactions of ? and ? fragments, apometallothionein, and zinc metallothionein with Cd2+. J Biol Chem 262, 4538-4548.

    Google Scholar 

  • Uchida Y, Takio K, Titani K et al. 1991 The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein. Neuron 7, 337-347.

    Google Scholar 

  • Vašák M, Hasler DW. 2000 Metallothioneins: New funtional and structure insights. Curr Opin Biotech 4, 177-183.

    Google Scholar 

  • Vašák M, Hasler DW, Faller P. 2000 Metal-thiolate clusters in neuronal growth inhibitory factor (GIF). J Inorg Biochem 79, 7-10.

    Google Scholar 

  • Winge DR, Miklossy KA. 1982 Differences in the polymorphic forms of metallothionein. Arch Biochem Biophys 214, 80-88.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing, 210093, China

    Yan-bo Shi, Liang Du & Wen-xia Tang

  2. State Key Laboratory of Pharacentical Biothnology, Department of Biochemistry, Nanjing University, Nanjing, 210093, China

    Wei-juan Zheng

Authors
  1. Yan-bo Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei-juan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-xia Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, Yb., Du, L., Zheng, Wj. et al. Isolation of GIF from porcine brain and studies of its zinc transfer kinetics with apo-carbonic anhydrase. Biometals 15, 421–427 (2002). https://doi.org/10.1023/A:1020220812484

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020220812484

Search

Navigation