A cyclic peptide analogue of loop III of PDGF‐BB causes apoptosis in human fibroblasts

FEBS Letters

Patel, Geeta¹  Scully, Michael F¹  Kakkar, Vijay V¹  Brennand, David M¹ 

[1] Leopold Muller Laboratory, Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London SW3 6LR, UK

关键词: Apoptosis;    Cyclic peptide;    Platelet-derived growth factor;    Human dermal fibroblast;    PDGF;    platelet-derived growth factor;    EGF;    epidermal growth factor;    FGF;    fibroblast growth factor;    PBS;    phosphate-buffered saline;    DMEM;    Dulbecco's modified Eagle's medium;    FBS;    foetal bovine serum;   

DOI  :  10.1016/S0014-5793(97)01446-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A cyclic peptide analogue of platelet-derived growth factor-BB (PDGF-BB), P1 [⁷⁷IVRKK⁸¹-C-⁷³RKIE⁷⁶], has recently been shown to inhibit specifically [¹²⁵I]PDGF-BB/receptor binding, and PDGF-BB-induced DNA synthesis in cells expressing PDGF receptors. Here we demonstrate that P1 induces apoptosis in exponentially growing human fibroblasts as confirmed by characteristic changes in cell and nuclear morphology, by TUNEL staining and by flow cytometry. Following incubation with P1 (100 μM), the percentage of cells exhibiting DNA fragmentation increased from 24% after 8 h to 76% after 28 h as exponentially growing cells progressed through the cell cycle. We conclude from these findings taken together that apoptosis accounts for the major proportion of P1-induced cell death. Omission of the Cys residue from P1 or replacement by Ser did not alter the potency of the peptide confirming that peptide dimerisation is not important for its activity. PDGF-BB, EGF, FGF, thrombin and foetal bovine serum were not able to rescue cells from the effects of P1. P1 is a useful tool for investigation of the balance of cellular proliferation/apoptosis in wound healing, atherosclerosis and restenosis, and constitutes a basis from which to design compounds with greater potency.

【 授权许可】

Unknown