Induction of Apoptosis in Vascular Smooth Muscle Cells by Heme Oxygenase-1-Derived Carbon Monoxide

Shu-Hui Juan, Lee Young Chau

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Heme oxygenase (HO) is the rate-limiting enzyme to catalyze the heme degradation, leading to the generation of biliverdin, which is subsequently converted to antioxidant bilirubin by biliverdin reductase,1,2 free iron, and carbon monoxide (CO). Three HO isozymes derived from distinct genes were identified.3 Among them, HO-1 is a stress-responsive protein and can be induced by a variety of oxidative-inducing agents, including heme, heavy metals, UV radiation, cytokines, and endotoxin.4,5 Recently, numerous in vitro and in vivo studies have demonstrated that the induction of HO-1 represents an important cellular protective mechanism against oxidative injury.4,5 In addition to the antioxidant effect of bilirubin,6–8 increasing interest has been drawn on the potential effects of CO. It has been shown that CO shares similar properties with nitric oxide (NO) to act as a putative neural transmitter in central nervous system and a potent vasodilator to regulate the vascular tone through the activation of soluble guanylate-cyclase-cGMP pathway.9–11 Both gases also exert potent anti-proliferative effect on vascular smooth muscle cells (VSMCs).12–15 Very recently, there are studies demonstrating that low concentration of CO provides protection against hyperoxic lung injury in animal16 and apoptotic death in fibroblasts and endothelial cells induced by TNF-α.17,18 Furthermore, a study on macrophages has shown that CO exhibits anti-inflammatory effect through a pathway involving the mitogen-activated protein kinases.19 It is apparent that CO mediates some of the beneficial effects of HO-1 induction under certain circumstances.
Original languageEnglish
Title of host publicationHeme Oxygenase in Biology and Medicine
EditorsNader G. Abraham
Place of PublicationBoston, MA
PublisherSpringer US
Pages449-457
Number of pages9
ISBN (Print)978-1-4615-0741-3
DOIs
Publication statusPublished - 2002

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    Juan, S-H., & Chau, L. Y. (2002). Induction of Apoptosis in Vascular Smooth Muscle Cells by Heme Oxygenase-1-Derived Carbon Monoxide. In N. G. Abraham (Ed.), Heme Oxygenase in Biology and Medicine (pp. 449-457). Springer US. https://doi.org/10.1007/978-1-4615-0741-3_40