Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells |
| |
Authors: | Shafqat J Juntti-Berggren L Zhong Z Ekberg K Köhler M Berggren P O Johansson J Wahren J Jörnvall H |
| |
Institution: | (1) Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm (Sweden), Fax + 46 8 337 462, e-mail: Hans.Jornvall@mbb.ki.se, SE;(2) The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden), SE;(3) Department of Surgical Sciences, Karolinska Institutet, 171 77 Stockholm (Sweden), SE |
| |
Abstract: | Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide
and related molecules on the intracellular Ca2+ concentration (Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide
(positions 27–31, EGSLQ), but not the des (27–31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in
Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no Ca2+]i response, and those with Ala at positions 2–5 induce responses with different amplitudes. These results define a species
cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells
with pertussis toxin abolishes the effect on Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and
activation of Na+,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.
Received 13 May 2002; accepted 16 May 2002 |
| |
Keywords: | : Proinsulin C-peptide Intracellular Ca2+ Hormonal response Peptide analogues Fura-2/AM Pertussis toxin Species cross-reacitivity |
本文献已被 PubMed SpringerLink 等数据库收录! |
|