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Effect of N 1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis

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Abstract

An unusual amino acid, hypusine [N ε-(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 N 1-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 μM caused almost complete inhibition of cellular hypusine synthesis and led to cytostasis of HUVEC. Pretreatment of HUVEC with GC7 up to 50 μM 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 μM) 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.

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Authors and Affiliations

  1. Cancer Research Institute, Catholic Research Institutes of Medical Science, The Catholic University of Korea, Seoul, 137-701, Korea

    Yoon Lee, Hyun-Kyung Kim, Hyo-Eun Park & Young Ae Joe

  2. Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, MD, 20892-4340, USA

    Myung Hee Park

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  1. Yoon Lee
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Lee, Y., Kim, HK., Park, HE. et al. Effect of N 1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis. Mol Cell Biochem 237, 69–76 (2002). https://doi.org/10.1023/A:1016535217038

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