血红素加氧酶-1在过氧化氢诱导的血管内皮生长因子合成中的作用：血红素加氧酶-1基因敲除的影响

Role of heme oxygenase-1 in hydrogen peroxide-induced VEGF synthesis: effect of HO-1 knockout.

作者信息

Cisowski Jarosław, Loboda Agnieszka, Józkowicz Alicja, Chen Sifeng, Agarwal Anupam, Dulak Józef

机构信息

Faculty of Biotechnology, Jagiellonian University, Kraków, Poland.

出版信息

Biochem Biophys Res Commun. 2005 Jan 21;326(3):670-6. doi: 10.1016/j.bbrc.2004.11.083.

DOI:10.1016/j.bbrc.2004.11.083

PMID:15596152

Abstract

Hydrogen peroxide is an important mediator of intracellular signaling, which potently enhances the expression of heme oxygenase-1 (HO-1) and upregulates synthesis of vascular endothelial growth factor (VEGF). The purpose of the present study was to explore the involvement of HO-1 in regulation of H(2)O(2)-mediated induction of VEGF synthesis. We provide genetic evidence that basal and H(2)O(2)-induced VEGF synthesis is partially dependent on HO-1. Inhibition of HO-1 activity by tin protoporphyrin (SnPPIX) resulted in downregulation of VEGF synthesis in murine fibroblasts and human keratinocytes. The relationship between HO-1 and VEGF was corroborated by using cells derived from HO-1 knockout mice, which demonstrated lower basal and H(2)O(2)-induced production of VEGF. Additionally, knock out of HO-1 gene impaired induction of VEGF by hemin, lysophosphatidylcholine, and prostaglandin-J(2). Our results provide confirmation for the involvement of HO-1 in regulation of angiogenesis.

摘要

过氧化氢是细胞内信号传导的重要介质，它能有效增强血红素加氧酶-1（HO-1）的表达并上调血管内皮生长因子（VEGF）的合成。本研究的目的是探讨HO-1在调节过氧化氢介导的VEGF合成诱导中的作用。我们提供了遗传学证据，表明基础状态和过氧化氢诱导的VEGF合成部分依赖于HO-1。锡原卟啉（SnPPIX）抑制HO-1活性导致小鼠成纤维细胞和人角质形成细胞中VEGF合成下调。通过使用来自HO-1基因敲除小鼠的细胞证实了HO-1与VEGF之间的关系，这些细胞显示出基础状态下以及过氧化氢诱导的VEGF产生较低。此外，敲除HO-1基因会损害血红素、溶血磷脂酰胆碱和前列腺素-J2对VEGF的诱导作用。我们的结果证实了HO-1参与血管生成的调节。