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

47 Citations (Scopus)

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

Fingerprint

C-Peptide
Kidney
Rats
Fura-2
Pertussis Toxin
Cell membranes
GTP-Binding Proteins
Adenosine Triphosphatases
Chemical activation
Cell Membrane
Peptides
Molecules

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

Cite this

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

Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells. / Shafqat, J.; Juntti-Berggren, L.; Zhong, Z.; Ekberg, K.; Köhler, M.; Berggren, P. O.; Johansson, J.; Wahren, J.; Jörnvall, H.

In: Cellular and Molecular Life Sciences, Vol. 59, No. 7, 01.07.2002, p. 1185-1189.

Research output: Contribution to journalArticle

Shafqat, J, Juntti-Berggren, L, Zhong, Z, Ekberg, K, Köhler, M, Berggren, PO, 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, vol. 59, no. 7, pp. 1185-1189. https://doi.org/10.1007/s00018-002-8496-5
Shafqat, J. ; Juntti-Berggren, L. ; Zhong, Z. ; Ekberg, K. ; Köhler, M. ; Berggren, P. O. ; Johansson, J. ; Wahren, J. ; Jörnvall, H. / Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells. In: Cellular and Molecular Life Sciences. 2002 ; Vol. 59, No. 7. pp. 1185-1189.
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