Abstract
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 microM), 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 com...Continue Reading
References
Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Apr 3, 1992·Cell·G I EvanD C Hancock
Apr 2, 1992·Nature·M C Raff
Jan 1, 1991·Annual Review of Cell Biology·R E EllisH R Horvitz
Jan 11, 1991·Cell·H J YehT F Deuel
Mar 1, 1991·Cell Proliferation·S V LennonT G Cotter
Apr 1, 1991·Journal of Cellular Biochemistry·G F PierceA Thomason
Apr 1, 1991·Journal of Cellular Biochemistry
Jun 1, 1991·Journal of Medicinal Chemistry·M G HindsJ A Robinson
Apr 20, 1990·Cell·A Ullrich, J Schlessinger
Nov 15, 1990·Biochemical and Biophysical Research Communications·S ArakiH Hayashi
Jul 1, 1990·Biochemical Pharmacology·N G RichardsJ A Robinson
Jul 6, 1989·Nature·M EilersJ M Bishop
Jul 18, 1986·Cell·R RossD F Bowen-Pope
Jun 9, 1988·Nature·M C RaffM D Noble
Jan 1, 1987·Annual Review of Cell Biology·T F Deuel
Aug 1, 1972·British Journal of Cancer·J F KerrA R Currie
Dec 1, 1983·Experimental and Molecular Pathology·W A ThomasJ Schmee
Oct 1, 1994·The Journal of Cell Biology·F ReF Colotta
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·H R KimT F Deuel
Aug 1, 1995·Circulation Research·M R BennettS M Schwartz
Jun 1, 1995·Circulation·J M IsnerJ Passeri
Mar 10, 1995·Science·H Steller
Sep 1, 1993·Molecular Biology of the Cell·J E MeredithM A Schwartz
Jan 1, 1993·Growth Factors·C H HeldinB Westermark
Mar 1, 1993·Immunology Today·J J Cohen
Jan 1, 1996·Molecular and Cellular Biology·G A PrestonJ C Barrett
Jan 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·Y J GengP Libby
Jan 15, 1997·The EMBO Journal·E K EvansS Kornbluth
Apr 1, 1997·The EMBO Journal·E Bossy-WetzelM Yaniv
Aug 11, 1997·FEBS Letters·D M BrennandG Patel
Citations
Jul 21, 1999·Herz·H Rupp, B Maisch
Dec 10, 2015·EJNMMI Research·Dan LiHong Shan
Jun 21, 2016·EBioMedicine·Xingqi WangQiang Xu
Jan 27, 2004·Journal of Vascular Surgery·Michael J EnglesbeAlexander W Clowes
Mar 20, 2004·Developmental Biology·Melanie Van StryKaren Symes
Jun 20, 2012·The Journal of Pharmacology and Experimental Therapeutics·Zhi-Ming HaoHong-Hong Li
Oct 31, 2020·Advances in Wound Care·Milena DeptułaMichał Pikuła