The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase.

Tenhunen, Raimo; Marver, Harvey S.; Schmid, Rudi

doi:10.1073/pnas.61.2.748

Cited by 1,607 publications

(1,102 citation statements)

References 17 publications

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“…1C). HO-1 is a biologically protective enzyme induced in the face of multiple stressors that catabolizes free heme to produce known antiinflammatory and antioxidant molecules, CO, and bilirubin (Tenhunen et al 1968(Tenhunen et al , 1969Stocker et al 1987;Hayashi et al 1999;Otterbein et al 2000;Kirkby and Adin 2006;Wegiel et al 2013). We utilized the pharmacological agent CoPPIX to specifically induce HO-1 expression in utricles.…”

Section: Discussionmentioning

confidence: 99%

“…However, unlike some HSPs, HO-1 does not have chaperone activity. Instead HO-1 is an enzyme responsible for heme catabolism, the products of which include bilirubin, carbon monoxide (CO), and free iron (Tenhunen et al 1968(Tenhunen et al , 1969Wegiel et al 2013). Bilirubin and CO each have antioxidant and antiinflammatory properties (Stocker et al 1987;Hayashi et al 1999;Otterbein et al 2000;Kirkby and Adin 2006;Wegiel et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

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Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 −/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

View full text Add to dashboard Cite

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“…Changes in the metabolism of iron/heme could be linked to hypoxiainduced erythropoietin and increased demand for iron for hemoglobin synthesis, although we have not seen the inductive expression of erythropoietin and hemoglobin. HO-1 is also one of the rate-limiting enzymes in heme catabolism and cleaves heme to form biliverdin IXa, carbon monoxide (CO) and iron (Tenhunen et al, 1968;Yoshida and Kikuchi, 1978). Its expression can be strongly induced by a variety of physiological and pathophysiological stimuli in human cells, including heme, heavy metals, inflammatory cytokines, nitric oxide and UV irradiation (Yoshida and Kikuchi, 1978;Keyse and Tyrrell, 1989;Takahashi et al, 1996;Otterbein and Choi, 2000).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of hypoxia-induced genes in Carassius auratus blastulae embryonic cells using suppression subtractive hybridization

Zhong

Wang

Zhang

et al. 2009

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…Haem oxygenase (HO) is the rate-limiting enzyme in haem degradation; this reaction produces biliverdin, which is subsequently converted to bilirubin by biliverdin reductase in biological systems (Tenhunen et al, 1968). Haem oxygenase -2 (HO-2) is the constitutive isoform of HO and is highly expressed in testis and brain under physiological conditions (Manies, 1997).…”

mentioning

confidence: 99%

Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour

et al. 2003

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Induction of haem oxygenase-1 (HO-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HO-1 in solid tumour with a focus on the antiapoptotic activity of HO-1. Treatment of rat hepatoma AH136B cells with the HO inhibitor zinc protoporphyrin IX (ZnPP IX) or tin protoporphyrin IX resulted in extensive apoptotic changes of tumour cells both in vivo and in vitro. Caspase-3 activity of the ZnPP IX-treated hepatoma cells increased significantly. Moreover, ZnPP IX-induced apoptosis was completely inhibited by simultaneous incubation with a specific caspase-3 inhibitor and was partially abrogated by bilirubin, a reaction product of HO. In vivo ZnPP IX treatment did not affect nitric oxide (NO) production and tumour blood flow. Western blot analyses showed that HO-1 expression in AH136B cells was strongly upregulated by NO donors, for example, S-nitroso-N-acetyl penicillamine and propylamine NONOate in vitro; conversely, it was remarkably reduced in vivo by pharmacological blockade of NOS. We conclude that HO-1 may function in antiapoptotic defense of the tumour, and thus it may have important protective and beneficial effects for tumour cells against oxidative stress induced by NO, which is produced in excess during solid tumour growth in vivo.

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The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase.

Cited by 1,607 publications

References 17 publications

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Identification and characterization of hypoxia-induced genes in Carassius auratus blastulae embryonic cells using suppression subtractive hybridization

Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour

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