Heme oxygenase/carbon monoxide signaling path-ways: Regulation and functional significance

Ryter, Stefan W.; Otterbein, Leo E.; Morse, Danielle; Choi, Augustine M.K.

doi:10.1007/978-1-4615-1087-1_29

Cited by 191 publications

(295 citation statements)

References 172 publications

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“…HO cleaves the α-meso carbon bridge of heme, yielding equimolar quantities of carbon monoxide (CO), Fe 2+ ions, and biliverdin. 15,16) The overexpression of HO-1 has been reported to augment apoptosis in breast cancer 17) and astroglia, 18) and our present data support a facilitatory role of HO-1 in apoptosis. Alternatively, the anti-apoptotic effects of HO-1 have been reported colon cancer, 19) thyroid cancer, 20) and gastric cancer.…”

Section: Discussionsupporting

confidence: 83%

Vitamin K3 Analogs Induce Selective Tumor Cytotoxicity in Neuroblastoma

Kitano

Yoda

Tabata

et al. 2012

Biological & Pharmaceutical Bulletin

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Section: Discussionsupporting

confidence: 83%

Vitamin K3 Analogs Induce Selective Tumor Cytotoxicity in Neuroblastoma

Kitano

Yoda

Tabata

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Generally, several antiapoptotic effects attributed to HO-1 are thought to be CO mediated (Ryter et al, 2002). This might also apply to Adora A 2A , because overexpression of HO-1 as well as exposure of RAW264.7 macrophages to CO augmented Adora A 2A mRNA as well as protein level (Haschemi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

Weis

Weigert

Knethen

et al. 2009

MBoC

151

128

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Apoptotic cells (AC) are rapidly engulfed by professional phagocytes such as macrophages to avoid secondary necrosis and thus inflammation. Recognition of AC polarizes macrophages toward an anti-inflammatory phenotype, which shows homology to an alternatively activated M2 macrophage. However, mechanistic details provoking these phenotype alterations are incompletely understood. Here, we demonstrate a biphasic up-regulation of heme oxygenase-1 (HO-1), a protein that bears an antiapoptotic as well as an anti-inflammatory potential, in primary human macrophages, which were exposed to the supernatant of AC. Although the first phase of HO-1 induction at 6 h was accomplished by AC-derived sphingosine-1-phosphate (S1P) acting via S1P receptor 1, the second wave of HO-1 induction at 24 h was attributed to autocrine signaling of vascular endothelial growth factor A (VEGFA), whose expression and release were facilitated by S1P. Whereas VEGFA release from macrophages was signal transducer and activator of transcription (STAT) 1-dependent, vascular endothelial growth factor itself triggered STAT1/STAT3 heterodimer formation, which bound to and activated the HO-1 promoter. Knockdown of HO-1 proved its relevance in facilitating enhanced expression of the antiapoptotic proteins Bcl-2 and Bcl-X L , as well as the anti-inflammatory adenosine receptor A 2A . These findings suggest that HO-1, which is induced by AC-derived S1P, is critically involved in macrophage polarization toward an M2 phenotype.

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“…Nitric oxide (NO) and carbon monoxide (CO) are involved in a wide array of biological processes (Moncada et al 1991, Ryter et al 2002. The biochemical pathways leading to NO formation from L-arginine have been associated with three NO synthase (NOS) isoforms differing in subcellular localization, regulation, and biological function (Palmer et al 1988).…”

Section: Introductionmentioning

confidence: 99%

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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Heme oxygenase/carbon monoxide signaling path-ways: Regulation and functional significance

Cited by 191 publications

References 172 publications

Vitamin K3 Analogs Induce Selective Tumor Cytotoxicity in Neuroblastoma

Vitamin K3 Analogs Induce Selective Tumor Cytotoxicity in Neuroblastoma

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

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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