Role of redox‐active metals in the regulation of the metallothionein and heme oxygenase genes by heme and hemopexin

Smith, Ann

doi:10.1002/9783527613700.ch05

Cited by 8 publications

(6 citation statements)

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“…These findings support a relationship between the amount of heme presented to the liver and net HPX turnover; and implicated, for the first time, a role for hepatic heme levels in HPX regulation . Consistent with these observations, heme induces HPX mRNA in murine hepatoma cells (Smith, 1999 ) and primary embryonic rat neurons (He et al, 2010 ). From other studies but relevant here, raising plasma heme did not alter the half-life of HSA as it does HPX.…”

Section: Improving Animal Models Of Human Disease In Which Hemopexin mentioning

confidence: 58%

“…This model is based on data from rhesus monkeys given heme i.v. (Foidart et al, 1982 ), HPX metabolism studies in humans (Foidart et al, 1983 ), known induction of HPX by heme (Smith, 1999 ; He et al, 2010 ), normal recycling of HPX after heme delivery (Smith and Morgan, 1978 , 1979 ), and HPX catabolism after i.v. administration of heme several fold higher than the binding capacity of HPX (Sears, 1970 ; Lane et al, 1972 ).…”

Section: The Clinical Relevance Of Hemoglobin Hemopexin and Haptoglmentioning

confidence: 99%

“…A HPX deficiency state develops in 60% of 8 months old HO1 −/− mice, while both Hp and HPX mRNA are increased in the liver. HPX mRNA increases in the liver lysates of HO1 −/− mice even by 7 weeks of age and HPX mRNA was also detected at extra-hepatic sites, e.g., in the spleen and kidney, likely due to induction by heme (Smith, 1999 ) or perhaps the inflammatory cytokine, IL-6 (Tolosano et al, 1996 ). Although, low plasma HPX and high hepatic HPX mRNA may appear discordant (Vinchi et al, 2008 ; Kovtunovych et al, 2010 ), the HO1 −/− mice likely have high hepatic heme levels; in which case there is no anomaly because high levels of hepatic heme increase HPX catabolism without compensatory HPX synthesis by the liver as shown in humans with hemolytic anemia and in rhesus monkeys (see Section Heme Toxicity and Hemopexin Deficiency States).…”

Section: The Clearance Of Hemoglobin By Hemopexin and Haptoglobin Durmentioning

confidence: 99%

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Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

2015

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The goal here is to describe our current understanding of heme metabolism and the deleterious effects of “free” heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of hemopexin (HPX). Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease (SCD), and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp) is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular (IVH) inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as SCD, sepsis, hemolytic-uremic syndrome, and conditions involving IVH and extravascular hemolysis (EVH), such as that generated by extracorporeal circulation during cardiopulmonary bypass (CPB) and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX, and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e., “replenishment”) therapies for patients with heme toxicity due to HPX depletion.

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Section: Improving Animal Models Of Human Disease In Which Hemopexin mentioning

confidence: 58%

Section: The Clinical Relevance Of Hemoglobin Hemopexin and Haptoglmentioning

confidence: 99%

Section: The Clearance Of Hemoglobin By Hemopexin and Haptoglobin Durmentioning

confidence: 99%

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Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

2015

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“…Heme (iron-protoporphyrin IX) is a component of haemoglobin, myoglobin and some enzymes such as cytochrome, heme peroxidase and others (Smith, 1999). It is released mainly after the destruction of red blood cells.…”

Section: Hemopexinmentioning

confidence: 99%

Acute phase proteins in sheep and goats – function, reference ranges and assessment methods: An overview

Iliev¹,

Georgieva²

2018

BJVM

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“…Its spatial structure is determined by two disulfide bonds connecting structurally related domains (C- and N-terminal) and binding the heme moiety [ 27 ]. Hpx plays a role in iron homeostasis by binding heme released into serum and then transporting it to the liver where it is disintegrated [ 28 , 29 ]. The half-life of Hpx in serum is 7 days.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

Pukajło-Marczyk

Zwołińska

2021

JCM

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Hemopexin (Hpx) is considered a factor in the pathogenesis of idiopathic nephrotic syndrome (INS). The aim of the study was to evaluate the serum and urine values of Hpx (sHpx and uHpx) in children with INS, analyze the role of Hpx, and assess its usefulness as a marker of the disease course. 51 children with INS and 18 age-matched controls were examined. Patients were divided into subgroups depending on the number of relapses (group IA—the first episode of INS, group IB—with relapses) and according to method of treatment (group IIA treated with gluco-corticosteroids (GCS), group IIB treated with GCS and other immunosuppressants). Hpx concentrations were determined by enzyme-linked immunosorbent assay (ELISA). sHpx and uHpx values in relapse were elevated in the whole INS group versus controls (p < 0.000). In remission their levels decreased, but still remained higher than in the control group (p < 0.000). In group IB uHpx levels were increased during remission as compared to group IA (p < 0.006). No significant impact of immuno-suppressants on sHpx was observed, but uHpx excretion in group IIA was higher in relapse (p < 0.026) and lower in remission (p < 0.0017) as compared to group IIB. The results suggest the role of Hpx in the pathogenesis of INS. Hpx may be a useful indicator for continuation of treatment, but it requires confirmation by further controlled studies.

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Role of redox‐active metals in the regulation of the metallothionein and heme oxygenase genes by heme and hemopexin

Cited by 8 publications

References 137 publications

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

Acute phase proteins in sheep and goats – function, reference ranges and assessment methods: An overview

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

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