Coexpression of erythropoietin and heme oxygenase genes in Hep3B cells

Lutton, John D.; Griffin, M.; Nishimura, Miki; Levere, Richard D.; Kappas, Attallah; Abraham, Nader G.; Shibahara, Shigeki

doi:10.1002/hep.1840170517

Cited by 4 publications

(4 citation statements)

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“…20 For example, exposure of Hep3B cells to heme, CoCl 2 , and SnPPIX resulted in a potent HO-1-independent induction of erythropoietin. 34 In THP-1 monocytes heme, ZnMPIX, ZnDPPIX, and CoPPIX, regardless of their effects on HO-1, reduced the transduction of interferon-␥ signal, whereas SnPPIX enhanced it and elevated expression of MHC-II. 35 Of importance, it has been shown that CoPPIX, SnPPIX, and ZnPPIX are direct inhibitors of caspase-3 and caspase-8, and thereby, they decrease the rate of apoptosis, independently of the HO-1 pathway.…”

Section: Discussionmentioning

confidence: 97%

Overexpression of Heme Oxygenase-1 in Murine Melanoma

Waś

Cichoń²,

Smolarczyk³

et al. 2006

The American Journal of Pathology

171

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Heme oxygenases (HOs) catalyze the oxidation of heme to the biologically active products carbon monoxide (CO), biliverdin, and ferrous iron. Two distinct variants of HOs have been described in humans and rodents, each encoded by a different gene: HO-2, which is constitutively expressed, and HO-1, which is potently induced in many cell types by heme, inflammatory cytokines, and oxidative stress-related factors.

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Section: Discussionmentioning

confidence: 97%

Overexpression of Heme Oxygenase-1 in Murine Melanoma

Waś

Cichoń²,

Smolarczyk³

et al. 2006

The American Journal of Pathology

171

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“…It must be kept in mind, however, that many effects of pharmacologic HO-1 inhibitors [ e.g ., SnPPIX, ZnPPIX, zinc mesoporphyrin (ZnMPIX), ZnDPIX], as well as HO-1 activators ( e.g ., heme, CoPPIX, CoCl 2 ), are HO-1 independent, because all these compounds display strong, unspecific functions (66, 93). For example, exposure of Hep3B cells to heme, CoCl 2 , and SnPPIX resulted in a potent, HO-1-independent induction of erythropoietin (99). Similar effects have been observed in endothelial cells, in which CoPPIX upregulated synthesis of proangiogenic and proinflammatory cytokine IL-8.…”

Section: Ho-1 Inhibition As a Potential Therapeutic Strategymentioning

confidence: 99%

Heme Oxygenase-1 in Tumors: Is It a False Friend?

Józkowicz

Waś

Dulak

2007

Antioxidants & Redox Signaling

336

302

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Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to biologically active products: carbon monoxide (CO), biliverdin, and ferrous iron. It participates in maintaining cellular homeostasis and plays an important protective role in the tissues by reducing oxidative injury, attenuating the inflammatory response, inhibiting cell apoptosis, and regulating cell proliferation. HO-1 is also an important proangiogenic mediator. Most studies have focused on the role of HO-1 in cardiovascular diseases, in which its significant, beneficial activity is well recognized. A growing body of evidence indicates, however, that HO-1 activation may play a role in carcinogenesis and can potently influence the growth and metastasis of tumors. HO-1 is very often upregulated in tumor tissues, and its expression is further increased in response to therapies. Although the exact effect can be tissue specific, HO-1 can be regarded as an enzyme facilitating tumor progression. Accordingly, inhibition of HO-1 can be suggested as a potential therapeutic approach sensitizing tumors to radiation, chemotherapy, or photodynamic therapy. HEME OXYGENASE-1 (HO-1)HEME OXYGENASE (HO) is a microsomal enzyme catalyzing the first, rate-limiting step in degradation of heme and playing an important role in recycling of iron (103). It cleaves the α-meso carbon bridge of heme, yielding equimolar quantities of carbon monoxide (CO) and iron ions Fe 2+ and biliverdin (156). CO is then exhaled from the organisms through the lung (50). Free iron induces the expression of the iron-sequestering ferritin and activates FeATPase, an iron transporter, which decrease intracellular Fe 2+ content. Finally, biliverdin is converted by biliverdin reductase to bilirubin (144), which can be oxidized by cytochrome P450 enzymes, such as Cyp1A1, Cyp2B1, or Cyp2a5, or glucoronidated by UDPglucuronyl-transferase and subsequently eliminated as bilirubin glucoronides by the biliaryfecal pathway (25).The enzymatic activity of HO results in decreased oxidative stress, attenuated inflammatory response, and a lower rate of apoptosis (Fig. 1). This is due to removal of heme, a potent prooxidant and proinflammatory agent, but also because of generation of biologically active products. Among them, CO is an important cellular messenger, with the signaling function resembling that of nitric oxide (NO). Like NO, CO induces soluble guanylyl cyclase (sGC) and thereby inhibits platelet aggregation, decreases leukocyte adhesion, and reduces endothelial cell apoptosis. In addition, it exerts antiinflammatory effects by inhibition of tumor necrosis factor (TNF), interleukin-1β (IL-1β), and macrophage inflammatory protein-1β (MIP-1β), or by upregulation of interleukin-10 (IL-10) (123). Ferrous iron, the © Mary Ann Liebert, Inc. Address reprint requests to: Alicja Jozkowicz, Ph.D., D.Sc., Department of Medical Biotechnology, Faculty of Biophysics, Biochemistry and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland, E-mail:alicia@mol.uj.edu.pl. Europe PMC Funders Gr...

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“…Heme is a natural substrate of HO known to cause elevation of HO-1 mRNA and activity . Heme caused 40-to 60-fold elevation in HO-1 mRNA, which significantly increased HO activity within 2 h [Lutton et al, 1993]. Experiments were performed to measure the effect of heme (10 µM) on HO activity in transfected and nontransfected EC.…”

Section: As Shown Inmentioning

confidence: 99%

“…Angiogenesis can be the response of various stress conditions, tissue injury [Odekon et al, 1992;Aubrey et al, 1996], ischemia, and solid tumor growth (Polverini and Leibovich, 1984]. Upregulation of the HO-1 gene was observed by several angionic stimulating factors, such as interleukin-1 and -6 (IL-1, IL-6), tumor necrosis factor (TNF), and transforming growth factor-␤ (TGF-␤) [Lutton et al, 1993;Neil et al, 1995]. Several transcriptional motives, such as NF-B, STAT, AP-1, and AP-2, have been shown to activate the HO-1 promoter and upregulate HO-1 gene expression Lavrovsky et al, 1996].…”

Section: As Shown Inmentioning

confidence: 99%

Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis

et al. 1998

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Heme oxygenase (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that induce oxidative injury such as hemoglobin/heme, hypoxia-ischemia and cytokines. Overexpression of HO-1 in endothelial cells (EC) might, therefore, protect against oxidative stress produced under these pathological conditions, by generation of CO, a vasodilator, and bilirubin, which has antioxidant properties that enhance blood vessel formation to counteract hypoxia-induced injury. A plasmid containing the cytomegalovirus promoter (pCMV) neomycin human HO-1 gene complexed to cationic liposomes, lipofectin, was used to transfect rabbit coronary microvessel EC. Cells transfected with human HO-1 gene demonstrated a twofold increase in HO activity and maintained a similar phenotype as in the nontransfected cells. Cell number in transfected cells with human HO-1 gene increased by about 45%, as compared to nontransfected or those transfected with control pCMV. Transfected and nontransfected EC revealed a similar response to basic fibroblast growth factor (bFGF) in capillary formation. However, transfected cells with the human HO-1 gene exhibited a twofold increase in blood vessel formation. The angiogenic response of EC to overexpression of HO-1 gene provides direct evidence that the inductive form of HO-1 following injury represents an important tissue adaptive mechanism for moderating the severity of cell damage produced in inflammatory reaction sites of hemorrhage, thrombosis and hypoxic-ischemia. Thus, HO-1 may participate in the regulation of EC activation, proliferation and angiogenesis.

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Coexpression of erythropoietin and heme oxygenase genes in Hep3B cells

Cited by 4 publications

References 37 publications

Overexpression of Heme Oxygenase-1 in Murine Melanoma

Overexpression of Heme Oxygenase-1 in Murine Melanoma

Heme Oxygenase-1 in Tumors: Is It a False Friend?

Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis

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