[feed] Atom [feed] RSS 1.0 [feed] RSS 2.0

Aruna, B. and Islam, A. and Ghosh, S. and Singh, A.K. and Vijayalakshmi, M. and Ahmad, F. and Ehtesham, N.Z. (2008) Biophysical Analyses of Human Resistin: Oligomer Formation Suggests Novel Biological Function. Biochemistry, 47 (47). pp. 12457-12466. ISSN 0006-2960

[img] Text
Biochemistry 47 p12457.pdf
Restricted to Repository staff only

Download (1317Kb) | Request a copy

Abstract

Resistin, a small secreted peptide initially identified as a link between obesity and diabetes in mice, was shown to be involved in mediating inflammation in humans. We had shown earlier that recombinant human resistin has a tendency to form aggregates by formation of inter/intramolecular disulfide linkages and that it undergoes a concentration-dependent conformational change in secondary structure from α-helical to β-sheet form. Here we report that this change in secondary structural conformation is due to the increase in the oligomeric form of human resistin as a function of protein concentration. Gel filtration analysis under different conditions further demonstrated that recombinant human resistin exists as a mixture of oligomer and trimer but is converted to a mixture of monomer and oligomer in the presence of 100 mM NaCl. We show that while the trimeric form of human resistin is stable to urea-induced denaturation, it is highly susceptible to NaCl and NaF, indicating the importance of ionic interactions in stabilization of trimer. In addition, urea was able to destabilize the oligomers indicating the involvement of hydrophobic interactions in oligomerization. Ionic as well as hydrophobic interactions stabilize the monomeric human resistin. Our data suggest that human resistin exists predominantly as oligomer and trimer in vitro. The oligomeric form of human resistin shows more potent effect on stimulation of proinflammatory cytokines. Therefore, it is very tempting to propose that the structural conformation of resistin may be involved in maintaining the very fine balance in regulation of macrophage function for successful response to a variety of pathological conditions

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 17 Nov 2015 09:07
Last Modified: 17 Nov 2015 09:07
URI: http://cdfd.sciencecentral.in/id/eprint/644

Actions (login required)

View Item View Item