Effect of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis.
An unusual amino acid, hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine], is formed post-translationally in a single cellular protein, the eukaryotic translation initiation factor 5A (eIF5A) by deoxyhypusine synthase and deoxyhypusine hydroxylase. Although eIF5A and its hypusine modification are essential for eukaryotic cell viability, the true physiological function of eIF5A is yet unknown. We have examined the effects of N1-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor of deoxyhypusine synthase, on endothelial cell proliferation, differentiation and apoptosis. Upon treatment of human umbilical vein endothelial cells (HUVEC) with GC7, dose-dependent inhibition of hypusine formation and cellular proliferation was observed. GC7 at 10 microM caused almost complete inhibition of cellular hypusine synthesis and led to cytostasis of HUVEC. Pretreatment of HUVEC with GC7 up to 50 microM for 4 days had little effect on the attachment and differentiation of these cells on Matri-gel and did not cause induction of apoptosis. Instead, the GC7 pretreatment (96 h at 5-50 microM) elicited protective effects against apoptotic death of HUVEC induced by serum starvation. These results suggest that eIF-5A may be involved in expression of proteins essential for apoptosis of endothelial cells as well as those for cellular proliferation.
Lee
Yoon
Y
Cancer Research Institute, The Catholic University of Korea, Seoul.
Kim
Hyun-Kyung
HK
Park
Hyo-Eun
HE
Park
Myung Hee
MH
Joe
Young Ae
YA
D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D010448:Peptide Initiation Factors / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000494:pharmacology; D016601:RNA-Binding Proteins; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D000097574:Eukaryotic Translation Initiation Factor 5A
D003094:Collagen; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007797:Laminin; D008239:Lysine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010448:Peptide Initiation Factors; D011509:Proteoglycans; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C059485:matrigel; C100028:hypusine; C063507:deoxyhypusine synthase