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

被引:0
|
作者
J. Shafqat
L. Juntti-Berggren
Z. Zhong
K. Ekberg
M. Köhler
P.-O. Berggren
J. Johansson
J. Wahren
H. Jörnvall
机构
[1] Department of Medical Biochemistry and Biophysics,
[2] Karolinska Institutet,undefined
[3] 171 77 Stockholm (Sweden),undefined
[4] Fax + 46 8 337 462,undefined
[5] e-mail: Hans.Jornvall@mbb.ki.se,undefined
[6] The Rolf Luft Center for Diabetes Research,undefined
[7] Department of Molecular Medicine,undefined
[8] Karolinska Institutet,undefined
[9] 171 77 Stockholm (Sweden),undefined
[10] Department of Surgical Sciences,undefined
[11] Karolinska Institutet,undefined
[12] 171 77 Stockholm (Sweden),undefined
来源
Cellular and Molecular Life Sciences CMLS | 2002年 / 59卷
关键词
Key words: Proinsulin C-peptide; Intracellular Ca2+; Hormonal response; Peptide analogues; Fura-2/AM; Pertussis toxin; Species cross-reacitivity.;
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摘要
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.
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页码:1185 / 1189
页数:4
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