Proteins as Sensitive Biomarkers of Human Conditions Associated with Oxidative Stress

Dalle‐Donne, Isabella; Rossi, Ranieri; Ceciliani, Fabrizio; Giustarini, Daniela; Colombo, Roberto; Milzani, Aldo

doi:10.1002/0471973122.ch16

Cited by 23 publications

(37 citation statements)

References 128 publications

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“…Dityrosine has been proposed as a biomarker of organism oxidative stress status or of cumulative exposure of proteins to oxidation both in vitro and in vivo (44). Dityrosine cross-linking products have been shown for example in the heme-binding protein neuroglobin upon oxidative stress (28).…”

Section: Discussionmentioning

confidence: 99%

Iron-mediated Oxidation Induces Conformational Changes within the Redox-sensing Protein HbpS

Lucana

Roscher

Honigmann

et al. 2010

Journal of Biological Chemistry

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HbpS is an extracellular oligomeric protein, which has been shown to act in concert with the two-component system SenSSenR during the sensing of redox stress. HbpS can bind and degrade heme under oxidative stress conditions, leading to a free iron ion. The liberated iron is subsequently coordinated on the protein surface. Furthermore, HbpS has been shown to modulate the phosphorylation state of the sensor kinase SenS as, in the absence of oxidative stress conditions, HbpS inhibits SenS autophosphorylation whereas the presence of heme or iron ions and redox-stressing agents enhances it. Using HbpS wild type and mutants as well as different biochemical and biophysical approaches, we show that iron-mediated oxidative stress induces both secondary structure and overall intrinsic conformational changes within HbpS. We demonstrate in addition that HbpS is oxidatively modified, leading to the generation of highly reactive carbonyl groups and tyrosine-tyrosine bonds. Further examination of the crystal structure and subsequent mutational analyses allowed the identification of the tyrosine residue participating in dityrosine formation, which occurs between two monomers within the octomeric assembly. Therefore, it is proposed that oxidative modifications causing structural and conformational changes are responsible for the control of SenS and hence of the HbpS-SenS-SenR signaling cascade.Iron is the fourth most abundant element in the Earth's crust and is an essential trace mineral for nearly all known organisms. Under physiological conditions, it exists either in the reduced Fe 2ϩ (ferrous) or in the oxidized Fe 3ϩ (ferric) form. It plays a crucial role in many biological processes, as photosynthesis, N 2 fixation, H 2 production and consumption, respiration, oxygen transport, or gene regulation. Because of its redox potential ranging from Ϫ300 to ϩ700 mV, iron is a versatile prosthetic component that can be incorporated into proteins either as a mono-or binuclear species, or in a more complex form as part of iron-sulfur clusters or heme groups (1-3).In the presence of oxygen, iron ions frequently lead to the formation of redox stress by the generation of reactive oxygen species ( ROS can provoke the damage of DNA, lipids, and proteins (4 -6). For instance, when proteins are exposed to ROS, they undergo a variety of oxidative modifications including: Nitration of aromatic amino acid residues, hydroxylation of aromatic groups, and aliphatic amino acid side-chains, sulfoxidation of methionine residues, and conversion of some amino acid residues to carbonyl derivatives. Oxidation can also induce the cleavage of the polypeptide chain and the formation of crosslinked protein derivatives (7,8). These modifications can lead to functional changes of proteins that subsequently disturb the cellular metabolism. Thus, while bacteria and other organisms have to ensure that enough iron ions are present for the diverse biochemical reactions, they also have to avoid their harmful effects.We have previously identified the two-component sy...

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Section: Discussionmentioning

confidence: 99%

Iron-mediated Oxidation Induces Conformational Changes within the Redox-sensing Protein HbpS

Lucana

Roscher

Honigmann

et al. 2010

Journal of Biological Chemistry

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“…The usefulness of the ideal biomarker of oxidative damage lies in its ability to provide a valid and early indication of disease and/or its progression [for reviews, see Dalle-Donne and coworkers (1,21 )]. Glutathione is the major low-molecular-mass thiol in mammals, and it plays a key role in cell resistance against oxidative and nitrosative damage by providing enzymes involved in the metabolism of ROS with reducing equivalents, by eliminating potentially toxic oxidation products, and by reducing oxidized or nitrosated protein thiols.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the effectiveness of these molecules compared with other "fingerprinting molecules" of oxidative stress, we treated human blood with increasing concentrations of t-BOOH, diamide, and menadione and verified the effect on GSSG and PSSG as well as on PCO and MDA concentrations. PCO and MDA were chosen because they are among the most widely used indicators of oxidative stress (21 ). Our data (Fig.…”

Section: Measurement Of Gssg and Pssg To Reveal Oxidative Stressmentioning

confidence: 99%

Oxidized Forms of Glutathione in Peripheral Blood as Biomarkers of Oxidative Stress

et al. 2006

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Background: Reduced glutathione (GSH) and its redox forms, glutathione disulfide (GSSG) and glutathionylated proteins (PSSG), are biomarkers of oxidative stress, but methodologic artifacts can interfere with their measurement. We evaluated the importance of correct sample handling during the preanalytical phase for GSH, GSSG, and PSSG measurement. Methods: We used human blood for in vitro experiments with oxidants [tert-butylhydroperoxide (t-BOOH), diamide, and menadione]. For in vivo experiments, we used rats in which we cannulated the jugular and femoral veins for both oxidant administration and blood collection. We measured GSH, GSSG, and PSSG with HPLC with or without sample pretreatment with N-ethylmaleimide (NEM) to prevent artifacts. We also measured malondialdehyde (MDA) with HPLC, and protein carbonyls (PCO) with spectrophotometric procedures. Results: When methodologic artifacts were prevented by pretreatment with NEM, GSSG results increased up to 3-fold over the basal concentrations, even in the presence of 5 mol/L t-BOOH or diamide and 20 mol/L menadione. PSSG increased by ϳ50% at 20 mol/L t-BOOH or diamide and at 50 mol/L menadione. PCO and MDA remained unchanged. In vivo oxidation treatments elicited immediate and significant increases in GSSG and PSSG over basal values (up to 200-fold), whereas PCO and MDA showed only slight variation 120 or 180 min after treatment. Conclusions: With the use of artifact-free measurement methods, GSH, GSSG, and PSSG are potentially powerful and reliable biomarkers of oxidative stress status

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“…Among the various aldehydes formed, malondialdehyde (MDA) is the most studied in the pathologic molecular process in oxidative stress. [15][16][17][18] The commonly employed approach to analyze MDA is by the thiobarbituric acid (TBA) test, that forms the adduct TBA 2 -MDA which has an absorption at 532 nm, allowing spectrophotometrically quantification. However, TBA reacts with a variety of oxidized lipids and aldehydes, sucrose, and urea, forming the known TBA-reactive substances (TBARS) that could cause an overestimation of the TBA 2 -MDA in colorimetric assay.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Oxidative Stress in Patients with Acute Lymphoblastic Leukemia: Experimental Evidence of the Efficacy of MDA as Cancer Biomarker in Young Patients

Almeida

Carrilho

Nixdorf

2017

J. Braz. Chem. Soc.

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Acute lymphoblastic leukemia (ALL) is a fatal disorder in most cases and is the most common cancer in young patients. ALL features an uncontrolled proliferation and maturation arrest of lymphoid progenitor cells (lymphoblast) in the bone marrow. An increase of reactive species production occurs in ALL with an involvement of oxidative stress (OS) and cellular damage. However, there is a lack of information about variations in young patients. The biomarker widely used to measure the OS is the main product of lipid peroxidation, the malondialdehyde (MDA). This biomarker, when evaluated by a chromatographic method and the data analyzed by multivariate analysis with other biochemical parameters of ALL patient charts, shows the distinction of healthy and ALL patients, and a great correlation with the risk of disease.

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Proteins as Sensitive Biomarkers of Human Conditions Associated with Oxidative Stress

Cited by 23 publications

References 128 publications

Iron-mediated Oxidation Induces Conformational Changes within the Redox-sensing Protein HbpS

Iron-mediated Oxidation Induces Conformational Changes within the Redox-sensing Protein HbpS

Oxidized Forms of Glutathione in Peripheral Blood as Biomarkers of Oxidative Stress

Evaluation of Oxidative Stress in Patients with Acute Lymphoblastic Leukemia: Experimental Evidence of the Efficacy of MDA as Cancer Biomarker in Young Patients

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