Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance

Silva, Rafael Cardoso Maciel Costa; Travassos, Leonardo H.; Paiva, Cláudia N.; Bozza, Marcelo T.

doi:10.1371/journal.ppat.1008599

Cited by 25 publications

(18 citation statements)

References 126 publications

(167 reference statements)

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“…The role of heme-induced oxidative stress in malaria pathogenesis has been validated in different in vivo studies using knockout mice lacking the gene for HO-1. HO-1 breaks down heme into biliverdin and carbon monoxide (CO), which are antioxidants ( Silva et al, 2020 ), and iron, which can be bound by the iron-binding protein ferritin ( Balla et al, 2005 ). Expression of HO-1 in the context of Plasmodium infection is important in the prevention of cerebral malaria in mice ( Pamplona et al, 2007 ).…”

Section: Oxidative Stress and The Pathogenesis Of Malariamentioning

confidence: 99%

Oxidative Stress and Pathogenesis in Malaria

Vasquez

Zuniga

Rodrı́guez

2021

Front. Cell. Infect. Microbiol.

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Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to Plasmodium infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. Plasmodium has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in P. falciparum infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.

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Section: Oxidative Stress and The Pathogenesis Of Malariamentioning

confidence: 99%

Oxidative Stress and Pathogenesis in Malaria

Vasquez

Zuniga

Rodrı́guez

2021

Front. Cell. Infect. Microbiol.

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“…Here, we discuss the effects, after noninfectious insults, of HO-1 expression in different organs of the body. Although, HO-1 expression has already been shown to exert protection against infectious insults in many organs, in this latter case, the specific pathogen under discussion will have major impacts on HO-1 role as a host protective mechanism, since HO-1 expression might impact on pathogen burden as well [15,16].…”

Section: Introductionmentioning

confidence: 99%

Heme Oxygenase 1 in Vertebrates: Friend and Foe

Silva

Correa

2021

Cell Biochem Biophys

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HO-1 is the inducible form of the enzyme heme-oxygenase. HO-1 catalyzes heme breakdown, reducing the levels of this important oxidant molecule and generating antioxidant, anti-inflammatory, and anti-apoptotic byproducts. Thus, HO-1 has been described as an important stress response mechanism during both physiologic and pathological processes. Interestingly, some findings are demonstrating that uncontrolled levels of HO-1 byproducts can be associated with cell death and tissue destruction as well. Furthermore, HO-1 can be located in the nucleus, influencing gene transcription, cellular proliferation, and DNA repair. Here, we will discuss several studies that approach HO-1 effects as a protective or detrimental mechanism in different pathological conditions. In this sense, as the major organs of vertebrates will deal specifically with distinct types of stresses, we discuss the HO-1 role in each of them, exposing the contradictions associated with HO-1 expression after different insults and circumstances.

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“…The chronicity of the disease with diverse parasites suggests the development of an immunosuppressive process during the infection [ 143 ]. Notably, it was shown that the activity of HO-1 could interfere with the resistance process, both by the elimination of heme and by the products of this enzymatic reaction [ 144 ]. Thus, the induction of HO-1, on the one hand, impairs phagocytosis and, on the other, reduces the secretion of pro-inflammatory cytokines [ 143 ].…”

Section: Therapeutic Implications Of Ho Inhibitorsmentioning

confidence: 99%

Immune Modulation by Inhibitors of the HO System

Fernández-Fierro

Funes

Ríos

et al. 2020

IJMS

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The heme oxygenase (HO) system involves three isoforms of this enzyme, HO-1, HO-2, and HO-3. The three of them display the same catalytic activity, oxidating the heme group to produce biliverdin, ferrous iron, and carbon monoxide (CO). HO-1 is the isoform most widely studied in proinflammatory diseases because treatments that overexpress this enzyme promote the generation of anti-inflammatory products. However, neonatal jaundice (hyperbilirubinemia) derived from HO overexpression led to the development of inhibitors, such as those based on metaloproto- and meso-porphyrins inhibitors with competitive activity. Further, non-competitive inhibitors have also been identified, such as synthetic and natural imidazole-dioxolane-based, small synthetic molecules, inhibitors of the enzyme regulation pathway, and genetic engineering using iRNA or CRISPR cas9. Despite most of the applications of the HO inhibitors being related to metabolic diseases, the beneficial effects of these molecules in immune-mediated diseases have also emerged. Different medical implications, including cancer, Alzheimer´s disease, and infections, are discussed in this article and as to how the selective inhibition of HO isoforms may contribute to the treatment of these ailments.

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Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance

Cited by 25 publications

References 126 publications

Oxidative Stress and Pathogenesis in Malaria

Oxidative Stress and Pathogenesis in Malaria

Heme Oxygenase 1 in Vertebrates: Friend and Foe

Immune Modulation by Inhibitors of the HO System

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