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- Title
Proinsulin C-peptide and its analogues induce intracellular Ca<sup>2+</sup> increases in human renal tubular cells.
- Authors
Shafqat, J.; Juntti-Berggren, L.; Zhong, Z.; Ekberg, Z.; Köhler, M.; Berggren, P. -O.; Johansson, J.; Wahren, J.; Jörnvall, H.
- 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.
- Subjects
PROINSULIN; CELL membranes; HORMONES; KIDNEY tubules; ENZYMES; PERTUSSIS toxin
- Publication
Cellular & Molecular Life Sciences, 2002, Vol 59, Issue 7, p1185
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-002-8496-5