Determination of HEL (Hexanoyl-Lysine Adduct): A Novel Biomarker for Omega-6 PUFA Oxidation

Sakai, Kazuo; Kino, Satoko; Masuda, Aino; Takeuchi, Masao; Ochi, Tairin; Osredkar, Joško; Rejc, Barbara; Geršak, Ksenija; Ramarathnam, Narasimhan; Kato, Yoji

doi:10.1007/978-94-007-7920-4_5

Cited by 16 publications

(13 citation statements)

References 16 publications

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“…We further addressed the hypothesis of the presence of a higher oxidative stress in vivo , in brain mitochondria of RSV-treated mice, by analyzing the level of oxidative cellular damages ( Fig 8 ). Two markers of oxidative damages, the protein thiol (SH) content, a sensitive target of H2O2 oxidation [ 71 ], and the HEL and 4-HNE modifications, as biomarkers for the initial stage of peroxidation [ 72 ], were quantified by spectrophotometry and by Western blotting, respectively. While protein-SH content was slightly, not significantly, decreased in O RSV-treated mice (p = 0.058, Fig 8A ), HEL-peroxided protein level was significantly increased in Old RSV-treated mice ( Fig 8B , O Ctl vs O RSV p = 0.0104).…”

Section: Resultsmentioning

confidence: 99%

Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

Guéguen¹,

Desquiret-Dumas²,

Leman³

et al. 2015

PLoS ONE

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Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5μM), resveratrol stimulated complex I activity, whereas at high dose (50 μM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed.

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Section: Resultsmentioning

confidence: 99%

Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

Guéguen¹,

Desquiret-Dumas²,

Leman³

et al. 2015

PLoS ONE

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“…HEL is formed by oxidative modification by oxidized omega-6 fatty acids such as linoleic acid or arachidonic acid. HEL can be a useful biomarker for initial stages of lipid peroxidation [34]. Urinary levels of HEL were also found to be elevated in children with ASD [35], with a recent study by Yui et al showing that increased HEL is associated with decreased antioxidant capacity in children with ASD [36].…”

Section: Introductionmentioning

confidence: 99%

Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

et al. 2019

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Background: Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction, restricted interest and repetitive behavior. Oxidative stress in response to environmental exposure plays a role in virtually every human disease and represents a significant avenue of research into the etiology of ASD. The aim of this study was to explore the diagnostic utility of four urinary biomarkers of oxidative stress. Methods: One hundred and thirty-nine (139) children and adolescents with ASD (89% male, average age = 10.0 years, age range = 2.1 to 18.1 years) and 47 healthy children and adolescents (49% male, average age 9.2, age range = 2.5 to 20.8 years) were recruited for this study. Their urinary 8-OH-dG, 8-isoprostane, dityrosine and hexanoil-lisine were determined by using the ELISA method. Urinary creatinine was determined with the kinetic Jaffee reaction and was used to normalize all biochemical measurements. Non-parametric tests and support vector machines (SVM) with three different kernel functions (linear, radial, polynomial) were used to explore and optimize the multivariate prediction of an ASD diagnosis based on the collected biochemical measurements. The SVM models were first trained using data from a random subset of children and adolescents from the ASD group (n = 70, 90% male, average age = 9.7 years, age range = 2.1 to 17.8 years) and the control group (n = 24, 45.8% male, average age = 9.4 years, age range = 2.5 to 20.8 years) using bootstrapping, with additional synthetic minority over-sampling (SMOTE), which was utilized because of unbalanced data. The computed SVM models were then validated using the remaining data from children and adolescents from the ASD (n = 69, 88% male, average age = 10.2 years, age range = 4.3 to 18.1 years) and the control group (n = 23, 52.2% male, average age = 8.9 years, age range = 2.6 to 16.7 years). Results: Using a non-parametric test, we found a trend showing that the urinary 8-OH-dG concentration was lower in children with ASD compared to the control group (unadjusted p = 0.085). When all four biochemical measurements were combined using SVMs with a radial kernel function, we could predict an ASD diagnosis with a balanced accuracy of 73.4%, thereby accounting for an estimated 20.8% of variance (p < 0.001). The predictive accuracy expressed as the area under the curve (AUC) was solid (95% CI = 0.691–0.908). Using the validation data, we achieved significantly lower rates of classification accuracy as expressed by the balanced accuracy (60.1%), the AUC (95% CI = 0.502–0.781) and the percentage of explained variance (R2 = 3.8%). Although the radial SVMs showed less predictive power using the validation data, they do, together with ratings of standardized SVM variable importance, provide some indication that urinary levels of 8-OH-dG and 8-isoprostane are predictive of an ASD diagnosis. Conclusions: Our results indicate that the examined urinary biomarkers in combination may differentiate children with ASD from healthy peers to a significant extent. However, the etiological importance of these findings is difficult to assesses, due to the high-dimensional nature of SVMs and a radial kernel function. Nonetheless, our results show that machine learning methods may provide significant insight into ASD and other disorders that could be related to oxidative stress.

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“…Urinary DT and HEL have been proposed to serve as sensitive biomarkers of oxidation of proteins and lipids, respectively [ 13 , 14 , 15 , 16 ], and both of them are deleterious products generated by ROS action [ 11 , 12 ]. This pilot report demonstrates, for the first time, a significant decrease in HEL of urine of the participants after a forest walk, but not after an urban walk.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary dityrosine (DT) and hexanoyl-lysine (HEL) are known as deleterious products generated by ROS action in the body [ 11 , 12 ]. Many scientists have suggested they are sensitive biomarkers for detecting oxidation of proteins and lipids, respectively [ 13 , 14 , 15 , 16 ]. However, there was no report on how the levels of urinary DT or HEL change after a forest walk.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Forest Walk on Urinary Dityrosine and Hexanoyl-Lysine in Young People: A Pilot Study

Yamada

Sato

Horike

et al. 2020

IJERPH

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A few studies indicate exposure to forests may alleviate oxidative stress in the body. However, more evidence is needed to support this potentiality. The purpose of the current study aimed at examining whether there is any difference in urinary levels of oxidatively modified proteins or lipids—dityrosine (DT) and hexanoyl-lysine (HEL), respectively, after a forest or urban walk. The study was performed on 29 university students who took part in forest walks (Shinjo Village) in Okayama Prefecture of Japan and on 42 university students who took part in urban walks in the downtown area of Okayama City. Urine samples before and after the walks were analyzed for DT and HEL excretion. Air phytoncides during the walks were also measured. We found a decreased tendency in urinary DT and HEL (p < 0.05) in most participants after the forest walks, but not after the urban walks. We further found the total levels of air phytoncides in the forest field were 1.50 times higher compared with those in the urban field. This study suggests the possibility that regular immersion in a forest environment might contribute toward weakening of the oxidative modifications of proteins or lipids in the body.

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Determination of HEL (Hexanoyl-Lysine Adduct): A Novel Biomarker for Omega-6 PUFA Oxidation

Cited by 16 publications

References 16 publications

Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

Effects of a Forest Walk on Urinary Dityrosine and Hexanoyl-Lysine in Young People: A Pilot Study

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