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PubMed: 30324533

Title
Tyrosine residues of bovine serum albumin play an important role in protecting SH-SY5Y cells against heme/H<sub>2</sub>O<sub>2</sub>/NO<sub>2</sub><sup>-</sup>-induced damage.
Journal
Molecular and cellular biochemistry
Volume
454
Issue
None
Pages
57-66
Date
2019-04-01
Authors
Gao Z | Li H | Wang P | Wu J

Evidence 1771ae90aa
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Protein tyrosine nitration has been identified as a biomarker of oxidative stress, and the generation of 3-nitrotyrosine (3-NT) is often accompanied with the increasing of ROS and RNS under pathologic condition [14].

a(CHEBI:"3-nitrotyrosine") positiveCorrelation a(MESH:"Reactive Oxygen Species") View Subject | View Object

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Hematoma
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a(CHEBI:"3-nitrotyrosine") positiveCorrelation a(MESH:"Reactive Nitrogen Species") View Subject | View Object

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Hematoma
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a(MESH:"Reactive Nitrogen Species") positiveCorrelation a(CHEBI:"3-nitrotyrosine") View Subject | View Object

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Hematoma
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a(MESH:"Reactive Oxygen Species") positiveCorrelation a(CHEBI:"3-nitrotyrosine") View Subject | View Object

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Evidence 0f8afa2ceb
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As shown in Fig. 5a, significant amount of 3-NT emerged in cultures following heme/H2O2/NO2 − treatment for 24 h (red staining), indicating the strongest nitrative stress level.

a(CHEBI:"3-nitrotyrosine") positiveCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) positiveCorrelation a(CHEBI:"3-nitrotyrosine") View Subject | View Object

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Evidence c895abedbd
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The carbonyl contents (Fig. 4a) and MDA level (Fig. 4c) from heme/H2O2/NO2 −-treated cells were the highest under all conditions.

a(CHEBI:"carbonyl group") positiveCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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a(CHEBI:malonaldehyde) positiveCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) positiveCorrelation a(CHEBI:"carbonyl group") View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) positiveCorrelation a(CHEBI:malonaldehyde) View Subject | View Object

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Evidence 54c64e5e70
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Whereas at the doses of 3, 4, and 5 μM, heme significantly reduced the viability of cells, which was in agreement with an earlier study [1].

a(CHEBI:heme) negativeCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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bp(MESH:"Cell Survival") negativeCorrelation a(CHEBI:heme) View Subject | View Object

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Hematoma
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Evidence 9035689cb7
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Malondialdehyde (MDA) represents evidence of systemic oxidative stress and inflammation [31], and is commonly used to estimate the level of lipid peroxidation.

a(CHEBI:malonaldehyde) positiveCorrelation bp(MESH:"Oxidative Stress") View Subject | View Object

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Hematoma
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a(CHEBI:malonaldehyde) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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Hematoma
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a(CHEBI:malonaldehyde) positiveCorrelation bp(MESH:"Lipid Peroxidation") View Subject | View Object

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Hematoma
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bp(MESH:"Lipid Peroxidation") positiveCorrelation a(CHEBI:malonaldehyde) View Subject | View Object

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bp(MESH:"Oxidative Stress") positiveCorrelation a(CHEBI:malonaldehyde) View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation a(CHEBI:malonaldehyde) View Subject | View Object

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Evidence 78659ad6b3
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The result showed that cell viability loss in a GO dose-dependent manner, and 1.5 mU mL−1 GO induced approximately 15% cell death after 24 h of treatment (Fig. 2b).

a(MESH:"Glucose Oxidase") negativeCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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bp(MESH:"Cell Survival") negativeCorrelation a(MESH:"Glucose Oxidase") View Subject | View Object

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Evidence c447be4d09
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Apoptosis has been found to be a major rout for the elimination of cells after a variety of stresses including ROS and RNS [30].

a(MESH:"Reactive Nitrogen Species") positiveCorrelation bp(MESH:Apoptosis) View Subject | View Object

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a(MESH:"Reactive Oxygen Species") positiveCorrelation bp(MESH:Apoptosis) View Subject | View Object

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bp(MESH:Apoptosis) positiveCorrelation a(MESH:"Reactive Oxygen Species") View Subject | View Object

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bp(MESH:Apoptosis) positiveCorrelation a(MESH:"Reactive Nitrogen Species") View Subject | View Object

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Hematoma
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Evidence d6f16ec394
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This result suggested that tyrosine residues of BSA may play an important role in heme detoxification.

p(HGNC:ALB, var("tyr")) decreases path(HM:"Heme cytotoxicity") View Subject | View Object

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Hematoma
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Discussion

Evidence cae801c5ba
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As illustrated in Fig. 2d, the loss of viability by heme/H2O2 and heme/H2O2/NO2 − was approximately 53 ± 3.8% and 65 ± 4.5%, respectively, which further confirmed that NO2 − dramatically enhances heme/ H2O2 toxicity.This result is well consistent with previous reports [3, 13].

bp(MESH:"Cell Survival") negativeCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme)) View Subject | View Object

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Hematoma
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bp(MESH:"Cell Survival") negativeCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme)) negativeCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) negativeCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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Hematoma
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Evidence 44cf27eca7
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As shown in Fig. 2d, heme/H2O2/ NO2−-induced loss of cell viability was significantly attenuated by BSA or BSA-T pretreatment, and BSA was more effective than BSA-T.

bp(MESH:"Cell Survival") positiveCorrelation p(HGNC:ALB) View Subject | View Object

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Hematoma
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bp(MESH:"Cell Survival") positiveCorrelation p(HGNC:ALB, pmod(Ph, Tyr)) View Subject | View Object

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Hematoma
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p(HGNC:ALB) positiveCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) positiveCorrelation bp(MESH:"Cell Survival") View Subject | View Object

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Hematoma
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Evidence 99ad2da821
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Figure 3a depicts the morphology of SHSY5Y cells after treated with various conditions. Compared with heme/H2O2 treatment, cells exposing to heme/ H2O2/NO2 − exacerbated cell apoptotic and reduced cell yield.

bp(MESH:Apoptosis) positiveCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) positiveCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Hematoma
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Evidence 12b4a5b1cf
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As quantified in Fig. 3c, although heme/H2O2/NO2 − increased the apoptotic rate to 32 ± 6.4%, BSA or BSA-T pretreatment caused a statistically significant reduced apoptotic rate (10 ± 5.0% and 15 ± 6.1%, respectively).

bp(MESH:Apoptosis) positiveCorrelation complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) View Subject | View Object

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Hematoma
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bp(MESH:Apoptosis) negativeCorrelation p(HGNC:ALB) View Subject | View Object

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Hematoma
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bp(MESH:Apoptosis) negativeCorrelation p(HGNC:ALB, pmod(Ph, Tyr)) View Subject | View Object

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Hematoma
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complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite)) positiveCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Hematoma
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p(HGNC:ALB) negativeCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) negativeCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Evidence e67e45a22e
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However, pretreatment with 2 μM BSA or BSA-T, we found that both BSA and BSA-T efficiently inhibited heme/H2O2/NO2 −- induced cell apoptotic and increased cell yields.

bp(MESH:Apoptosis) negativeCorrelation p(HGNC:ALB) View Subject | View Object

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Hematoma
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bp(MESH:Apoptosis) negativeCorrelation p(HGNC:ALB, pmod(Ph, Tyr)) View Subject | View Object

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Hematoma
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p(HGNC:ALB) decreases act(complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite))) View Subject | View Object

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Hematoma
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p(HGNC:ALB) negativeCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) decreases act(complex(a(CHEBI:"hydrogen peroxide"), a(CHEBI:heme), a(CHEBI:nitrite))) View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) negativeCorrelation bp(MESH:Apoptosis) View Subject | View Object

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Evidence 9b29eb8363
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Monzani et al. [10] also concluded that the heme-SA complex promotes H2O2 activation processes that bear the characteristics of enzymatic reactions and may have biological relevance.

complex(a(CHEBI:heme), p(HGNC:ALB)) increases act(a(CHEBI:"hydrogen peroxide")) View Subject | View Object

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Evidence d3489918b2
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Serum albumin (SA) can act as the heme scavenger by forming heme-SA complex [2, 4–8].

p(HGNC:ALB) decreases a(CHEBI:heme) View Subject | View Object

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Introduction

Evidence 3c7fe408a1
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Both BSA and BSA-T attenuated heme/H2O2/NO2 −-induced protein carbonylation and lipid peroxidation.

p(HGNC:ALB) decreases bp(MESH:"Protein Carbonylation") View Subject | View Object

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Hematoma
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p(HGNC:ALB) decreases bp(MESH:"Lipid Peroxidation") View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) decreases bp(MESH:"Protein Carbonylation") View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) decreases bp(MESH:"Lipid Peroxidation") View Subject | View Object

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Hematoma
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Evidence 48fe6b234f
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Of note, incubation with BSA or BSA-T for 24 h decreased heme/ H2O2/NO2 −-derived 3-NT deposits as compared with heme/ H2O2/NO2 − treatment alone, and BSA is more effective on suppressing the formation of 3-NT than BSA-T (Fig. 5b).

p(HGNC:ALB) decreases a(CHEBI:"3-nitrotyrosine") View Subject | View Object

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Hematoma
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p(HGNC:ALB, pmod(Ph, Tyr)) decreases a(CHEBI:"3-nitrotyrosine") View Subject | View Object

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Hematoma
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Evidence b6547ff747
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Furthermore, the cytoprotective effect of BSA was stronger than that of BSA-T (Fig. 5), suggesting that tyrosine residues of BSA act as oxidation target to prevent other important protein from heme-induced RNS associated damage.

p(HGNC:ALB, var("tyr")) decreases act(a(MESH:"Reactive Nitrogen Species")) View Subject | View Object

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Hematoma
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Discussion

Evidence 3a6a7f9e3f
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For this reason, it has been considered as a therapeutic tool to counteract heme toxic effects in severe hemolytic diseases, and the usefulness of SA therapy has already been demonstrated in a rat model of acute intracerebral hematoma [2, 9].

p(RGD:Alb) decreases path(HM:"Heme cytotoxicity") View Subject | View Object

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Introduction

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