• Advances in Traditional Medicine
• /
• 제4권3호
• /
• pp.211-214
• /
• 2004

The inhibitory effect of dl-puerol A as but-2-enolide isolated from Sophora japonica was investigated on copper ion-induced protein oxidative modification in vitro. It inhibited copper-induced protein oxidative modification. However, its inhibitory effect was a little weaker than that of $dl-{\alpha}-tocopherol$ as an antioxidant. The results demonstrated that dl-puerol A, one of but-2-enolides, might be of use in the oxidative stress.

• Bulletin of the Korean Chemical Society
• /
• 제34권2호
• /
• pp.406-410
• /
• 2013

Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

• BMB Reports
• /
• 제36권5호
• /
• pp.488-492
• /
• 2003

Neurofilament-L (NF-L) is a major element of neuronal cytoskeletons and known to be important for neuronal survival in vivo. Since oxidative stress might play a critical role in the pathogenesis of neurodegenerative diseases, we investigated the role of copper and peroxide in the modification of NF-L. When disassembled NF-L was incubated with copper ion and hydrogen peroxide, then the aggregation of protein was proportional to copper and hydrogen peroxide concentrations. Dityrosine crosslink formation was obtained in copper-mediated NF-L aggregates. The copper-mediated modification of NF-L was significantly inhibited by thiol antioxidants, N-acetylcysteine, glutathione, and thiourea. A thioflavin-T binding assay was performed to determine whether the copper/$H_2O_2$ system-induced in vitro aggregation of NF-L displays amyloid-like characteristics. The aggregate of NF-L displayed thioflavin T reactivity, which was reminiscent of amyloid. This study suggests that copper-mediated NF-L modification might be closely related to oxidative reactions which may play a critical role in neurodegenerative diseases.

• Bulletin of the Korean Chemical Society
• /
• 제34권11호
• /
• pp.3295-3300
• /
• 2013

Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

• BMB Reports
• /
• 제45권2호
• /
• pp.114-119
• /
• 2012

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (${\bullet}OH$) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification. Carnosine, and anserine were shown to significantly prevent salsolinol-mediated NF-L aggregation. Both compounds also inhibited the generation of ${\bullet}OH$ induced by salsolinol. The results indicated that carnosine and related compounds may prevent salsolinol-mediated NF-L modification via free radical scavenging.

• BMB Reports
• /
• 제46권2호
• /
• pp.119-123
• /
• 2013

Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin, is known to perform a role in the pathogenesis of Parkinson's disease (PD). In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with salsolinol. When cytochrome c was incubated with salsolinol, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in salsolinol-treated cytochrome c. Salsolinol also led to the release of iron from cytochrome c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the salsolinol-mediated cytochrome c modification and carbonyl compound formation. It is suggested that oxidative damage of cytochrome c by salsolinol might induce the increase of iron content in cells, subsequently leading to the deleterious condition which was observed. This mechanism may, in part, provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD.

• Molecules and Cells
• /
• 제25권3호
• /
• pp.347-351
• /
• 2008

Several lines of evidence indicate that the oxidative modification of protein and the subsequent accumulation of the modified proteins have been found in cells during aging, oxidative stress, and in various pathological states including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis. The important agents that give rise to the modification of a protein may be represented by reactive aldehydic intermediates, such as ketoaldehydes, 2-alkenals and 4-hydroxy-2-alkenals. These reactive aldehydes are considered important mediators of cell damage due to their ability to covalently modify biomolecules, which can disrupt important cellular functions and can cause mutations. Furthermore, the adduction of aldehydes to apolipoprotein B in low-density lipoproteins (LDL) has been strongly implicated in the mechanism by which LDL is converted to an atherogenic form that is taken up by macrophages, leading to the formation of foam cells. During the search for an endogenous inducer of cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin production during inflammation and immune responses, 4-hydroxy-2-noennal (HNE), one of the most representative lipid peroxidation product, has been identified as the potential inducer of COX-2. In addition, the following study on the molecular mechanism of the COX-2 induction by HNE has unequivocally established that a serum component, which is eventually identified to be denatured LDL, is essential for COX-2 induction. Here I review current understanding of the mechanisms by which HNE in cooperation with the serum component activates gene expression of COX-2.

• Bulletin of the Korean Chemical Society
• /
• 제28권1호
• /
• pp.77-80
• /
• 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.

• BMB Reports
• /
• 제45권3호
• /
• pp.147-152
• /
• 2012

Methylglyoxal (MG) was identified as an intermediate in non-enzymatic glycation and increased levels were reported in patients with diabetes. In this study, we evaluated the effects of MG on the modification of ferritin. When ferritin was incubated with MG, covalent crosslinking of the protein increased in a time- and MG dose-dependent manner. Reactive oxygen species (ROS) scavengers, $N-acetyl-_L-cysteine$ and thiourea suppressed the MG-mediated ferritin modification. The formation of dityrosine was observed in MG-mediated ferritin aggregates and ROS scavengers inhibited the formation of dityrosine. During the reaction between ferritin and MG, the generation of ROS was increased as a function of incubation time. These results suggest that ROS may play a role in the modification of ferritin by MG. The reaction between ferritin and MG led to the release of iron ions from the protein. Ferritin exposure to MG resulted in a loss of arginine, histidine and lysine residues. It was assumed that oxidative damage to ferritin caused by MG may induce an increase in the iron content in cells, which is deleterious to cells. This mechanism, in part, may provide an explanation or the deterioration of organs under diabetic conditions.

• Bulletin of the Korean Chemical Society
• /
• 제32권9호
• /
• pp.3421-3424
• /
• 2011

The endogenous neurotoxin, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), has been considered a potential causative factor for the pathogenesis of Parkinson's disease (PD). In this study, we examined oxidative modification of neurofilament-L (NF-L) induced by salsolinol. When disassembled NF-L was incubated with salsolinol, the aggregation of protein was increased with the concentration of sasolinol. The formation of carbonyl compound was obtained in salsolinol-mediated NF-L aggregates. This process was protected by free radical scavengers, such as N-acetyl-L-cysteine and glutathione. These results suggest that the aggregation of NF-L is mediated by salsolinol via the generation of free radicals. We also investigated the effects of copper ion on salsolinol-mediated NF-L modification. In the presence of copper ions, salsolinol enhanced the modification of NF-L. We suggest that salsolinol might be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of neurodegenerative diseases and related disorders.