Hydrogen peroxide induces up-regulation of Fas in human endothelial cells

Toshimitsu Suhara, Keisuke Fukuo, Tomosada Sugimoto, Shigeto Morimoto, Takeshi Nakahashi, Shigeki Hata, Masumi Shimizu, Toshio Ogihara

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Hydrogen peroxide (H2O2), an oxidant generated by inflammatory cells, is an important mediator of injury of endothelial cells (ECs). Here we show that H2O2 induces up-regulation of the expression of Fas, a death signal, in human ECs in culture. Flow cytometric analysis with a mAb against human Fas showed that incubation for 24 h with H2O2 induced a dose-dependent increase in the level of Fas in ECs. Coincubation with catalase, which rapidly degrades H2O2, inhibited H2O2-induced up-regulation of Fas. H2O2 also induced a dose-dependent increase in Fas mRNA level. A significant increase in Fas mRNA levels was observed from 6 h after stimulation with H2O2. Vanadate, a protein phosphatase inhibitor, significantly enhanced Fas mRNA and protein levels in H2O2-treated ECs. On the other hand, genistein, a tyrosine kinase inhibitor, inhibited H2O2- induced Fas mRNA expression. Furthermore, a flow cytometric method with propidium iodide staining and electron microscopic analysis showed that incubation with an agonistic Ab against Fas (anti-Fas IgM) induced apoptosis in H2O2-treated cells. These findings suggest that H2O2 induces up- regulation of Fas in ECs and that activation of protein tyrosine kinase may be involved in the mechanism of H2O2-induced Fas expression. Therefore, Fas-mediated apoptosis may have a pathologic role in H2O2-induced EC injury and thereby provide a new therapeutic target.

Original languageEnglish
Pages (from-to)4042-4047
Number of pages6
JournalJournal of Immunology
Volume160
Issue number8
Publication statusPublished - Apr 15 1998

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Hydrogen Peroxide
Up-Regulation
Endothelial Cells
Messenger RNA
Protein-Tyrosine Kinases
Apoptosis
Vanadates
Propidium
Genistein
Phosphoprotein Phosphatases
Wounds and Injuries
Oxidants
Catalase
Cell Culture Techniques
Electrons
Staining and Labeling
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Suhara, T., Fukuo, K., Sugimoto, T., Morimoto, S., Nakahashi, T., Hata, S., ... Ogihara, T. (1998). Hydrogen peroxide induces up-regulation of Fas in human endothelial cells. Journal of Immunology, 160(8), 4042-4047.

Hydrogen peroxide induces up-regulation of Fas in human endothelial cells. / Suhara, Toshimitsu; Fukuo, Keisuke; Sugimoto, Tomosada; Morimoto, Shigeto; Nakahashi, Takeshi; Hata, Shigeki; Shimizu, Masumi; Ogihara, Toshio.

In: Journal of Immunology, Vol. 160, No. 8, 15.04.1998, p. 4042-4047.

Research output: Contribution to journalArticle

Suhara, T, Fukuo, K, Sugimoto, T, Morimoto, S, Nakahashi, T, Hata, S, Shimizu, M & Ogihara, T 1998, 'Hydrogen peroxide induces up-regulation of Fas in human endothelial cells', Journal of Immunology, vol. 160, no. 8, pp. 4042-4047.
Suhara T, Fukuo K, Sugimoto T, Morimoto S, Nakahashi T, Hata S et al. Hydrogen peroxide induces up-regulation of Fas in human endothelial cells. Journal of Immunology. 1998 Apr 15;160(8):4042-4047.
Suhara, Toshimitsu ; Fukuo, Keisuke ; Sugimoto, Tomosada ; Morimoto, Shigeto ; Nakahashi, Takeshi ; Hata, Shigeki ; Shimizu, Masumi ; Ogihara, Toshio. / Hydrogen peroxide induces up-regulation of Fas in human endothelial cells. In: Journal of Immunology. 1998 ; Vol. 160, No. 8. pp. 4042-4047.
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