Biphasic induction of heme oxygenase-1 expression in macrophages stimulated with lipopolysaccharide

Srisook, Klaokwan; Cha, Young‐Nam

doi:10.1016/j.bcp.2004.07.001

Cited by 63 publications

(52 citation statements)

References 42 publications

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“…1B). HO-1 is an important stress-responsive antioxidant enzyme known to be induced by oxidative or electrophilic stimuli that can cause depletion of GSH (27,28). In agreement with this, the expression of HO-1 protein was increased significantly in PC12 cells as early as 4 h after exposure to SIN-1 (Fig.…”

Section: Increased Gclc Expression and Gsh Synthesis By Peroxynitritesupporting

confidence: 72%

Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling

Jang

et al. 2007

Journal of Biological Chemistry

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102

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Induction of heme oxygenase-1 (HO-1) expression has been associated with adaptive cytoprotection against a wide array of toxic insults, but the underlying molecular mechanisms remain largely unresolved. In this study, we investigated the potential role of carbon monoxide (CO), one of the by-products of the HO-1 reaction, in the adaptive survival response to peroxynitrite-induced PC12 cell death. Upon treatment of rat pheochromocytoma (PC12) cells with the peroxynitrite generator 3-morpholinosydnonimine hydrochloride (SIN-1), the cellular GSH level decreased initially, but was gradually restored to the basal level. This was accompanied by increased expression of the catalytic subunit of glutamate-cysteine ligase (GCLC), the rate-limiting enzyme in GSH biosynthesis. The SIN-1-induced GCLC up-regulation was preceded by induction of HO-1 and subsequent CO production. Inhibition of HO activity by zinc protoporphyrin IX or knockdown of HO-1 gene expression by small interfering RNA abrogated the up-regulation of GCLC expression and the subsequent GSH restoration induced by SIN-1. In contrast, additional exposure to the CO-releasing molecule (CO-RM) restored the GSH level previously reduced by inhibition of CO production using zinc protoporphyrin IX. Furthermore, CO-RM treatment up-regulated GCLC expression through activation of Nrf2. The CO-RM-induced activation of Nrf2 was under the control of the phosphatidylinositol 3-kinase/Akt signaling pathway. In conclusion, CO produced by HO-1 rescues PC12 cells from nitrosative stress through induction of GCLC, which is mediated by activation of phosphatidylinositol 3-kinase/Akt and subsequently Nrf2 signaling. Heme oxygenase (HO)2 is the rate-limiting enzyme involved in the oxidative degradation of free heme and produces biliverdin/bilirubin, free iron, and carbon monoxide (CO) (1). Of the two known isoforms of HO (i.e. HO-1 and HO-2), the expression of only HO-1 is induced in response to external stresses. Formerly known as the stress response protein HSP32 in rats, HO-1 confers cytoprotection against oxidative and inflammatory injuries caused by a wide array of noxious or pathogenic insults (2-4). In a previous study, we observed that up-regulation of HO-1 prevents the rat pheochromocytoma (PC12) cells from apoptotic death caused by peroxynitrite (5). CO produced by elevated HO activity has been found to be responsible, at least in part, for the anti-apoptotic function of up-regulated HO-1 (6 -8). However, the underlying mechanisms by which CO exerts the cytoprotective effects against peroxynitrite-induced cell death remain largely unresolved.CO is reported to increase the production of cGMP and to exert vasodilatory and anti-apoptotic effects (9). Liu et al. (7) reported that the anti-apoptotic function of CO is partially dependent on the activation of soluble guanylate cyclase in vascular smooth muscle cells. Furthermore, a recent study has revealed that the anti-apoptotic effect of CO is associated with activation of p38 mitogen-activated protein kinase (MAPK) (10). In t...

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Section: Increased Gclc Expression and Gsh Synthesis By Peroxynitritesupporting

confidence: 72%

Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling

Jang

et al. 2007

Journal of Biological Chemistry

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102

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“…The expression of both HO-1 and iNOS is induced following cell activation (Wiesel et al, 2000;Connelly et al, 2003;Srisook and Cha, 2004). In our RAW264.7 cells, we observed an inhibition of respiration even when iNOS activity was completely blocked by L-NIO, suggesting an NO-independent mechanism.…”

Section: Discussionmentioning

confidence: 52%

Inhibition of cellular respiration by endogenously produced carbon monoxide

D'Amico

Lam

Hagen

et al. 2006

Journal of Cell Science

120

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Endogenously produced nitric oxide (NO) interacts with mitochondrial cytochrome c oxidase, leading to inhibition of cellular respiration. This interaction has been shown to have important physiological and pathophysiological consequences. Exogenous carbon monoxide (CO) is also known to inhibit cytochrome c oxidase in vitro; however, it is not clear whether endogenously produced CO can inhibit cellular respiration and, if so, what the significance of this might be. In this study, we show that exogenous CO inhibits respiration in a moderate but persistent manner in HEK293 cells under ambient (21%) oxygen concentrations (Ki=1.44 μM). This effect of CO was increased (Ki=0.35 μM) by incubation in hypoxic conditions (1% oxygen). Endogenous CO, generated by HEK293 cells transfected with the inducible isoform of haem oxygenase (haem oxygenase-1; HO-1), also inhibited cellular respiration moderately (by 12%) and this was accompanied by inhibition (23%) of cytochrome c oxidase activity. When the cells were incubated in hypoxic conditions during HO-1 induction, the inhibitory effect of CO on cell respiration was markedly increased to 70%. Furthermore, endogenously produced CO was found to be responsible for the respiratory inhibition that occurs in RAW264.7 cells activated in hypoxic conditions with lipopolysaccharide and interferon-γ, in the presence of N-(iminoethyl)-L-ornithine to prevent the synthesis of NO. Our results indicate that CO contributes significantly to the respiratory inhibition in activated cells, particularly under hypoxic conditions. Inhibition of cell respiration by endogenous CO through its interaction with cytochrome c oxidase might have an important role in inflammatory and hypoxic conditions.

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“…Comparable results were obtained in mice liver (Rizzardini et al 1993), rat Kuppfer cells (Immenschuh et al 1999), macrophages (Srisook & Cha 2004), and rat glial cells (Kitamura et al 1998). As was also demonstrated in other tissues or cell types, the induction of this enzymatic activity is probably involved in the development of cytoprotective mechanisms triggered by both injury and infection (Ryter & Tyrrell 2000).…”

Section: Discussionmentioning

confidence: 68%

Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production

Grion¹,

Repetto²,

Pomeraniec³

et al. 2007

Journal of Endocrinology

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The present study was designed to investigate the effect of lipopolysaccharide (LPS) on the expression levels and activities of the nitric oxide synthase (NOS) and heme oxygenase (HO) systems in the rat adrenal gland. Both enzymatic activities were significantly increased in this tissue after in vivo treatment with LPS. The concurrent induction of the HO-1, NOS-1, and NOS-2 gene products was also detected as both mRNAs and protein levels were augmented by this treatment in a time-dependent way. A significant interaction between both signaling systems was also demonstrated as in vivo blockage of NOS activity with N(G)-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in HO expression and activity levels, while an increase in NOS activity was observed when HO was inhibited by Sn-protoporphyrin IX (Sn-PPIX). As both NOS and HO activities have been previously involved in the modulation of adrenal steroidogenesis, we investigated the participation of these signaling systems in the adrenal response to LPS. Our results showed that acute stimulation of steroid production by ACTH was significantly increased when either NOS or HO activities were inhibited. We conclude that adrenal NOS and HO can be induced by a non-lethal dose of endotoxin supporting a modulatory role for these activities in the adrenal response to immune challenges.

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Biphasic induction of heme oxygenase-1 expression in macrophages stimulated with lipopolysaccharide

Cited by 63 publications

References 42 publications

Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling

Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling

Inhibition of cellular respiration by endogenously produced carbon monoxide

Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production

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