Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells

J. Shafqat, L. Juntti-Berggren, Z. Zhong, K. Ekberg, M. Köhler, P. O. Berggren, J. Johansson, J. Wahren, H. Jörnvall

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1185-1189
Number of pages5
JournalCellular and Molecular Life Sciences
Volume59
Issue number7
DOIs
StatePublished - Jul 1 2002

Keywords

  • Fura-2/AM
  • Hormonal response
  • Intracellular Ca
  • Peptide analogues
  • Pertussis toxin
  • Proinsulin C-peptide
  • Species cross-reacitivity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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    Shafqat, J., Juntti-Berggren, L., Zhong, Z., Ekberg, K., Köhler, M., Berggren, P. O., Johansson, J., Wahren, J., & Jörnvall, H. (2002). Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells. Cellular and Molecular Life Sciences, 59(7), 1185-1189. https://doi.org/10.1007/s00018-002-8496-5