The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells

Mitani, Kinuko; Fujita, Hideaki; Fukuda, Yoshiaki; Kappas, Attallah; Sassa, Shigeru

doi:10.1042/bj2900819

Cited by 59 publications

(35 citation statements)

References 47 publications

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“…On the other hand, the effects of inhibition of protein synthesis differ with the activating agent and cell type. Cycloheximide blocks the TNF-␣-and IL-1␣-mediated expression of HO-1 in endothelial cells and prostaglandin A 2 induction of HO-1 in fibroblasts (6,54), has no effects on HO-1 induction by IL-6 in hepatoma cells (30) or LPS induction of HO-1 in macrophages (5), and even causes enhanced induction of HO-1 by cobalt protoporphyrin (31). Although reported to have no effects on the level of HO-1 mRNA (35, 54), we noticed a small but statistically significant increase in the expression of HO-1 transcript after treatment of endothelial cells with cycloheximide alone.…”

Section: Discussionmentioning

confidence: 99%

Rickettsia rickettsiiInfection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

et al. 2002

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Existing evidence suggests that oxidative insults and antioxidant defense mechanisms play a critical role in the host cell response during infection of endothelial cells by Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. Heme oxygenase (HO), a rate-limiting enzyme in the pathway for heme catabolism, protects against oxidant damage in a variety of stress situations. Here, we report on the expression of the inducible and constitutive HO isozymes, HO-1 and HO-2, during R. rickettsii infection of endothelial cells. Steady-state levels for HO-1 mRNA were increased two-to threefold, as early as 4 h postinfection, whereas HO-2 mRNA was not affected. Induction of HO-1 mRNA was dependent on the dose of infection and occurred in a time-dependent manner, reaching maximal levels at 4 to 7 h. The increase in HO-1 mRNA occurred at the level of trancription as it was blocked by the transcriptional inhibitors, actinomycin D and ␣-amanitin. Rickettsiae are obligate, intracellular parasites and causative agents of severe bacterial diseases of humans, including epidemic typhus and Rocky Mountain spotted fever, caused, respectively, by Rickettsia prowazekii and R. rickettsii. These bacteria are transmitted to their mammalian hosts by arthropod vectors such as ticks, fleas, lice, and mites and grow within the cytoplasm (and occasionally the nucleus) of eukaryotic cells (37,62). Rickettsiae exhibit a tropism for the endothelium and invade vascular endothelial cells as a major target. The proliferation of organisms in capillary endothelium and associated cytopathic effects of infection contribute to increased vascular permeability (57). Studies have suggested that the host endothelial cells actively respond to intracellular infection by altering the expression of several proteins, including tissue factor (50, 56), plasminogen activator inhibitor 1 (13, 44), E-selectin (12, 49), interleukin-1 (IL-1), 51). Ultrastructural studies have shown that infected endothelial cells sustain severe damage at late stages of infection, as indicated by dilatation of the rough endoplasmic reticulum and outer nuclear envelope, loss of osmoregulatory control, and cell lysis (45,46).The mechanisms of cell injury induced by R. rickettsii remain largely unknown. Based on the striking architectural changes in the cytoskeleton of infected cells, it was speculated that reactive oxygen species may be one of the major causes of cell injury by R. rickettsii. Subsequent biochemical analysis confirmed the accumulation of intracellular peroxides and superoxide radicals (42, 47), detection of higher amounts of extracellular hydrogen peroxide in the culture medium of infected cells (21), and reduction in levels of intracellular thiols (48). Further, the activities of three important enzymes of the cellular antioxidant system, namely, glucose-6-phosphate dehydrogenase, catalase, and glutathione peroxidase, were downregulated, while that of superoxide dismutase was increased in endothelial cells exposed to R. rickettsii (11,42). ␣-Lipoic acid...

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Section: Discussionmentioning

confidence: 99%

Rickettsia rickettsiiInfection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

et al. 2002

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“…An important signal induced by NO is heme oxygenase 1 (HO-1), a rate-limiting enzyme and a significant cytoprotective molecule produced under physiological conditions and by different stresses, including oxidative stress (21)(22)(23)(24)(25)(26)(27), endotoxemia (28), UV irradiation (29), heavy metals (30), heat shock (31), and NO (22)(23)(24)(25)(26)(27). The main function of HO-1 is to degrade heme to form Fe(II), biliverdin, and carbon monoxide (CO) (21).…”

Section: N Itric Oxide Produced By Inducible No Synthase (Inos)mentioning

confidence: 99%

Cytoprotective Function of Heme Oxygenase 1 Induced by a Nitrated Cyclic Nucleotide Formed during Murine Salmonellosis

Zaki

Fujii

Okamoto

et al. 2009

The Journal of Immunology

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Signaling mechanisms of NO-mediated host defense are yet to be elucidated. In this study, we report a unique signal pathway for cytoprotection during Salmonella infection that involves heme oxygenase 1 (HO-1) induced by a nitrated cyclic nucleotide, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP). Wild-type C57BL/6 mice and C57BL/6 mice lacking inducible NO synthase (iNOS) were infected with Salmonella enterica serovar Typhimurium LT2. HO-1 was markedly up-regulated during the infection, the level being significantly higher in wild-type mice than in iNOS-deficient mice. HO-1 up-regulation was associated with 8-nitro-cGMP formation detected immunohistochemically in Salmonella-infected mouse liver and peritoneal macrophages. 8-Nitro-cGMP either exogenously added or formed endogenously induced HO-1 in cultured macrophages infected with Salmonella. HO-1 inhibition by polyethylene glycol-conjugated zinc-protoporphyrin IX impaired intracellular killing of bacteria in mouse liver and in both RAW 264 cells and peritoneal macrophages. Infection-associated apoptosis was also markedly increased in polyethylene glycol-conjugated zinc-protoporphyrin IX-treated mouse liver cells and cultured macrophages. This effect of HO-1 inhibition was further confirmed by using HO-1 short interfering RNA in peritoneal macrophages. Our results suggest that HO-1 induced by NO-mediated 8-nitro-cGMP formation contributes, via its potent cytoprotective function, to host defense during murine salmonellosis.

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“…Haem oxygenase -2 (HO-2) is the constitutive isoform of HO and is highly expressed in testis and brain under physiological conditions (Manies, 1997). Haem oxygenase -1 (HO-1), the inducible isoform of HO, also known as heat shock protein 32 (HSP32), is found at low levels in most mammalian tissues, but it is constitutively expressed in liver and spleen and is upregulated by its substrate haem (Tenhunen et al, 1970) and various stress-inducing stimuli such as UV light (Keyse and Tyrrell, 1989), heavy metals (Mitani et al, 1993), heat shock (Shibahara et al, 1987), hypoxia (Motterlini et al, 2000), and nitric oxide (NO) (Kim et al, 1995;Foresti and Motterlini, 1999;Bouton and Demple, 2000). Induction of HO-1 is suggested to have a cytoprotective effect against oxidative injury (Dennery et al, 1997;, because some bile pigments formed via HO have been shown to behave as antioxidants (Minetti et al, 1998;Dore et al, 1999).…”

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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 role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells

Cited by 59 publications

References 47 publications

Rickettsia rickettsiiInfection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

Rickettsia rickettsiiInfection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

Cytoprotective Function of Heme Oxygenase 1 Induced by a Nitrated Cyclic Nucleotide Formed during Murine Salmonellosis

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

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