• Bulletin of the Korean Chemical Society
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• v.28 no.1
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• pp.77-80
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• 2007

As neurofilament proteins are major cytoskeletal components of neuron, abnormality of neurofilament is proposed in brain with neurodegenerative disorders such as Parkinson's disease (PD). Since oxidative stress might play a critical role in altering normal brain proteins, we investigated the oxidative modification of neurofilament-L (NF-L) induced by the reaction of cytochrome c with H2O2. When NF-L was incubated with cytochrome c and H2O2, the protein aggregation was increased in cytochrome c and H2O2 concentrationsdependent manner. Radical scavengers, azide, formate and N-acetyl cysteine, prevented the aggregation of NFL induced by the cytochrome c/H2O2 system. The formations of carbonyl group and dityrosine were obtained in cytochrome c/H2O2-mediated NF-L aggregates. Iron specific chelator, desferoxamine, prevented the cytochrome c/H2O2 system-mediated NF-L aggregation. These results suggest that the cytochrome c/H2O2 system may be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of PD and related disorders.

• Bulletin of the Korean Chemical Society
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• v.29 no.9
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• pp.1732-1736
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• 2008

The endogenous dipeptides, carnosine and related compounds, are the naturally occurring dipeptides with multiple neuroprotective properties. We have examined the protective effects of carnosine, homocarnosine and anserine on the aggregation of neurofilament-L (NF-L) induced by neurotoxin, acrolein. When NF-L was incubated with acrolein in the presence of carnosine, homocarnosine or anserine, protein aggregation was inhibited in a concentration-dependent manner. These compounds inhibited the formation of protein carbonyl compounds and dityrosine in acrolein-mediated NF-L aggregates. The aggregates of NF-L displayed thioflavin T reactivity, reminiscent of amyloid. This thioflavin T reactivity was inhibited by carnosine and related compounds. This effect was associated with decreased formation of oxidatively modified proteins. Our results suggested that carnosine and related compounds might have protective effects to brain proteins under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders.

• BMB Reports
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• v.40 no.1
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• pp.125-129
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• 2007

Neurofilament-L (NF-L) is a major element of the neuronal cytoskeleton and is essential for neuronal survival. Moreover, abnormalities in NF-L result in neurodegenerative disorders. Carnosine and the related endogeneous histidine dipeptides prevent protein modifications such as oxidation and glycation. In the present study, we investigated whether histidine dipeptides, carnosine, homocarnosine, or anserine protect NF-L against oxidative modification during reaction between cytochrome c and $H_2O_2$. Carnosine, homocarnosine and anserine all prevented cytochrome c/$H_2O_2$-mediated NF-L aggregation. In addition, these compounds also effectively inhibited the formation of dityrosine, and this inhibition was found to be associated with the reduced formations of oxidatively modified proteins. Our results suggest that carnosine and histidine dipeptides have antioxidant effects on brain proteins under pathophysiological conditions leading to degenerative damage, such as, those caused by neurodegenerative disorders.

• Molecules and Cells
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• v.22 no.2
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• pp.220-227
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• 2006

Oxidative alteration of mitochondrial cytochrome c has been linked to disease and is one of the causes of proapoptotic events. We have investigated the modification of cytochrome c by $H_2O_2$. When cytochrome c was incubated with $H_2O_2$, oligomerization of the protein increased and the formation of carbonyl derivatives and dityrosine was stimulated. Radical scavengers prevented these effects suggesting that free radicals are implicated in the $H_2O_2$-mediated oligomerization. Oligomerization was significantly inhibited by the iron chelator, deferoxamine. During incubation of deoxyribose with cytochrome c and $H_2O_2$, damage to the deoxyribose occurred in parallel with the release of iron from cytochrome c. When cytochrome c that had been exposed to $H_2O_2$ was analyzed by amino acid analysis, the tyrosine, histidine and methionine residues proved to be particularly sensitive. These results suggest that $H_2O_2$-mediated cytochrome c oligomerization is due to oxidative damage resulting from free radicals generated by a combination of the peroxidase activity of cytochrome c and the Fenton reaction of free iron released from the oxidatively-damaged protein.

• BMB Reports
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• v.49 no.1
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• pp.45-50
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• 2016

Salsolinol (SAL), a compound derived from dopamine metabolism, is the most probable neurotoxin involved in the pathogenesis of Parkinson's disease (PD). In this study, we investigated the modification and inactivation of human ceruloplasmin (hCP) induced by SAL. Incubation of hCP with SAL increased the protein aggregation and enzyme inactivation in a dose-dependent manner. Reactive oxygen species scavengers and copper chelators inhibited the SAL-mediated hCP modification and inactivation. The formation of dityrosine was detected in SAL-mediated hCP aggregates. Amino acid analysis post the exposure of hCP to SAL revealed that aspartate, histidine, lysine, threonine and tyrosine residues were particularly sensitive. Since hCP is a major copper transport protein, oxidative damage of hCP by SAL may induce perturbation of the copper transport system, which subsequently leads to deleterious conditions in cells. This study of the mechanism by which ceruloplasmin is modified by salsolinol may provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD. [BMB Reports 2016; 49(1): 45-50]

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.485-492
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• 2002

The molecular fate of thyroglobulin (Tg) is controlled by oligomerization, a means of storing Tg at high concentrations, and deoligomerization. The oligomerization of bovine Tg are intermolecular reactions that occur through oxidative processes, such as disulfide and dityrosine formation, as well as isopeptide formation; disulfide formation is primarily responsible for Tg oligomerization. Here, the protein disulfide isomerase (PDI) and/or peroxidase-induced oligomerization of unfolded thyroglobulins, which were prepared by treating bovine Tg with heat, urea or thiol/urea, was investigated using SDS-PAGE analyses. In addition, the enzymatic oligomerization was compared with non-enzymatic oligomerization. The thermally-induced oilgomerization of Tg, dependent on glutathione redox state, was affected by the ionic strength or the presence of a surfactant. Meanwhile, PDI-catalyzed oligomerization, time and pH-dependent, was the most remarkable with unfolded/reduced Tg, which was prepared from a treatment with urea/DTT, while the thermally-unfolded Tg was less sensitive. Similarly, the oligomerization of unfolded/reduced Tg was also mediated by peroxidase. However, PDI showed no remarkable effect on the peroxidase-mediated oligomerization of either the unfolded or unfolded/reduced Tg. Additionally, the reductive deoligomerization of oligomeric Tg was exerted by PDI in an excessively reducing state. Based on these results, it is proposed that PDI catalyzes the oligomerization of Tg through the disulfide linkage and its deoligomerization in the molecular fate, and this process may require a specific molecular form of Tg, optimally unfolded/reduced, in a proper redox state.

• Applied Chemistry for Engineering
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• v.32 no.2
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• pp.163-167
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• 2021

In the present work, we studied a method for the synthesis of uniform gold-peptide hierarchical superstructures using tyrosine rich peptide, Tyr-Tyr-Leu-Tyr-Tyr (YYLYY). Peptide nanoparticles self-assembled by dityrosine bonds were synthesized through the photo-crosslinking reaction of the peptide, and gold-peptide hybrid nanoparticles were synthesized using biomineralization properties of tyrosine in a green synthetic manner. The synthesized gold-peptide hybrid nanoparticles were then characterized by transmission electron microscopy, scanning electron microscopy, dynamic light scattering, UV-vis spectroscopy, scanning transmission electron microscopy-energy dispersive X-ray spectroscopy, and X-ray diffraction. Furthermore, the catalytic activity of gold-peptide hybrid nanoparticles was confirmed by the reduction reaction of methylene blue where the catalytic reaction rate constant was 13.4 × 10-3 s-1.