Effects of Fenton Reaction on Human Serum Albumin: An In Vitro Study

Khosravifarsani, Meysam; Monfared, Ali Shabestani; Pouramir, Mahdi; Zabihi, Ebrahim

doi:10.19082/2970

Cited by 17 publications

(15 citation statements)

References 20 publications

(27 reference statements)

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“…3A, 0 B and 0 C ) and H 2 O 2 only (Fig. 4) revealed some oxidative potential for both, although more for Fe 2ϩ , supported by a carbonylation assessment that indicated more ROS-based oxidative damage (42) in bulk enzyme extracts in T. reesei than in P. placenta (Table 1). This might reflect some potential for Fe 2ϩ to auto-oxidize in the presence of molecular oxygen, leading to the production of HO˙in the absence of H 2 O 2 (43).…”

Section: Resultsmentioning

confidence: 77%

Oxidative Damage Control during Decay of Wood by Brown Rot Fungus Using Oxygen Radicals

Castaño

Zhang

Anderson

et al. 2018

Appl Environ Microbiol

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Brown rot wood-degrading fungi deploy reactive oxygen species (ROS) to loosen plant cell walls and enable selective polysaccharide extraction. These ROS, including Fenton-generated hydroxyl radicals (HO˙), react with little specificity and risk damaging hyphae and secreted enzymes. Recently, it was shown that brown rot fungi reduce this risk, in part, by differentially expressing genes involved in HO˙ generation ahead of those coding carbohydrate-active enzymes (CAZYs). However, there are notable exceptions to this pattern, and we hypothesized that brown rot fungi would require additional extracellular mechanisms to limit ROS damage. To assess this, we grew directionally on wood wafers to spatially segregate early from later decay stages. Extracellular HO˙ production (avoidance) and quenching (suppression) capacities among the stages were analyzed, along with the ability of secreted CAZYs to maintain activity postoxidation (tolerance). First, we found that HO and Fe concentrations in the extracellular environment were conducive to HO˙ production in early (HO:Fe ratio 2:1) but not later (ratio 1:131) stages of decay. Second, we found that ABTS radical cation quenching (antioxidant capacity) was higher in later decay stages, coincident with higher fungal phenolic concentrations. Third, by surveying enzyme activities before/after exposure to Fenton-generated HO˙, we found that CAZYs secreted early, amid HO˙, were more tolerant of oxidative stress than those expressed later and were more tolerant than homologs in the model CAZY producer Collectively, this indicates that uses avoidance, suppression, and tolerance mechanisms, extracellularly, to complement intracellular differential expression, enabling this brown rot fungus to use ROS to degrade wood. Wood is one of the largest pools of carbon on Earth, and its decomposition is dominated in most systems by fungi. Wood-degrading fungi specialize in extracting sugars bound within lignin, either by removing lignin first (white rot) or by using Fenton-generated reactive oxygen species (ROS) to "loosen" wood cell walls, enabling selective sugar extraction (brown rot). Although white rot lignin-degrading pathways are well characterized, there are many uncertainties in brown rot fungal mechanisms. Our study addressed a key uncertainty in how brown rot fungi deploy ROS without damaging themselves or the enzymes they secrete. In addition to revealing differentially expressed genes to promote ROS generation only in early decay, our study revealed three spatial control mechanisms to avoid/tolerate ROS: (i) constraining Fenton reactant concentrations (HO, Fe), (ii) quenching ROS via antioxidants, and (iii) secreting ROS-tolerant enzymes. These results not only offer insight into natural decomposition pathways but also generate targets for biotechnological development.

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Section: Resultsmentioning

confidence: 77%

Oxidative Damage Control during Decay of Wood by Brown Rot Fungus Using Oxygen Radicals

Castaño

Zhang

Anderson

et al. 2018

Appl Environ Microbiol

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“…3,4 Through an in vitro experimental approach, we demonstrated that oxidation of Hb to MeHb was completely inhibited either by PRP, PPP or albumin. Considering that serum albumin is the most abundant plasma protein as well as a physiologic iron chelator and ROS scavenger, 9,10 it is conceivable that plasma albumin contributes to the anti-oxidative role of PRP. This could explain the therapeutic effect of intra-articular injection of PRP observed in patients with haemophilia.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood samples (3 mL) containing acid-citrate-dextrose (ACD) were obtained from healthy donors who provided informed written consent. Blood was centrifuged at 180 g for 10…”

Section: Preparation Of Lysed Erythrocytes Platelet-rich Plasma (Pmentioning

confidence: 99%

“…5,6 Based on these settings, preliminary in vitro and animal-based studies have postulated that intra-articular injection of iron-chelating drugs and reactive oxygen species (ROS) scavengers is a potential therapeutic tool for haemophilic joint damage. 7,8 Interestingly, it is well known that albumin, the most abundant plasma protein, is a physiological iron chelator and ROS scavenger 9,10 allowing us to hypothesize that the presence of plasma in synovial cavity reduces oxidation of Hb-coupled iron and the consequent cartilage damage. In this context, different clinical groups including us have recently reported that intra-articular injection of blood-derived autologous platelet-rich plasma (PRP) improves the Health Joint Haemophilia Score (HJHS) and reduces bleeding episodes and pain in patients with chronic haemophilic synovitis (CHS).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra‐articular injection of PRP in patients with chronic haemophilic synovitis

et al. 2020

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Introduction and Aim: Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS. Methods: Oxidation of haemoglobin (Hb) to methaemoglobin (MeHb) through Fenton reaction was induced in vitro by addition of potassium ferricyanide in the presence or absence of peripheral blood-derived platelets-rich or platelets-poor plasma (PRP/ PPP) or albumin. The relevance of in vitro findings was analysed in synovial fluid (SF) samples from one patient with CHS obtained before and after 6 months of PRP intraarticular injection. Results: MeHb formation was completely impaired either by of PPP, PRP or albumin indicating that PRP exerts an anti-oxidative effect, probably due by plasma albumin. Analysis of SF samples revealed the presence of MeHb levels and haemosiderinladen macrophages in SF obtained before PRP treatment. Reduction of synovial MeHb, normalization of cellular composition and improvement of health joint haemophilic score, pain and bleeding episodes were registered after 6 months of PRP intra-articular injection. Conclusion: Inhibition of Fenton reaction and the consequent normalization of joint cellular composition is a noncanonical mechanism underlying the therapeutic effect of PRP intra-articular injection in CHS. K E Y W O R D S haemophilia, methaemoglobin, platelets-rich plasma, PRP intra-articular injection, synovitis e188 | CAVIGLIA et AL.

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“…Lys-199 is among the amino acids involved in the intramolecular forces that stabilize ligands at site I [ 17 , 29 , 31 ]. As lysine is highly susceptible to carbonylation [ 45 ], the obtained alteration in the binding capacity provoked by Tau-NBr 2 cannot exclude the involvement of the modification of this amino-acid residue. In summary, we propose that the oxidation of Trp-214 and Lys-199 might be the main oxidative alterations provoked by Tau-NBr 2 at site I of HSA.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation

Bertozo

Neto

Ximenes

2018

IJMS

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Human serum albumin (HSA) is a target for reactive oxygen species (ROS), and alterations of its physiological functions caused by oxidation is a current issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are located at site I of HSA, were experimentally and computationally oxidized, and the effect on the binding constant with phenylbutazone was measured. HSA was submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic alterations in the protein which were consistent with the formation of N′-formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by Tau-NHCl, provoked a significant increase in the association constant with phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated by changing these residues using the putative oxidation products. Based on the Amber score function, the interaction energy was measured, and it showed that, while native HSA presented an interaction energy of −21.3 kJ/mol, HSA with Trp-214 altered to N′-formylkynurenine resulted in an energy of −28.4 kJ/mol, and HSA with Lys-199 altered to its carbonylated form resulted in an energy of −33.9 kJ/mol. In summary, these experimental and theoretical findings show that oxidative alterations of amino-acid residues at site I of HSA affect its binding efficacy.

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Effects of Fenton Reaction on Human Serum Albumin: An In Vitro Study

Cited by 17 publications

References 20 publications

Oxidative Damage Control during Decay of Wood by Brown Rot Fungus Using Oxygen Radicals

Oxidative Damage Control during Decay of Wood by Brown Rot Fungus Using Oxygen Radicals

Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra‐articular injection of PRP in patients with chronic haemophilic synovitis

Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation

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