The University of Tokyo · 의학
우치다 교수의 연구실은 지질 과산화 반응으로 생성되는 유해 산화성 알데하이드, 특히 아크로알레인과 4-하이드록시-2-논날(4-HNE)의 단백질 유도체 형성 메커니즘을 중심으로 연구를 전개하고 있습니다. 이들은 생체 내 산화 스트레스와 관련된 단백질 손상의 분자 기전을 규명하고, 특히 아미노산 잔기와의 공유 결합을 통해 단백질 기능 이상을 유도하는 메커니즘을 분석합니다. 또한 메틸글리옥살과 같은 당화 유도 산물의 단백질 변형과 그 생물학적 영향에 대해서도 연구하며, 항체 기반 진단 및 구조 분석을 통해 병태생리학적 의미를 규명하고자 합니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Acrolein (CH 2 =CH—CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein i
In the present study, we studied the signal transduction mechanism that is involved in the expression of c-Jun protein evident after exposure of rat liver epithelial RL34 cells to the major end product of oxidized fatty acid metabolism, 4-hydroxy-2-nonenal (HNE). HNE treatment of the cells resulted in depletion of intracellular glutathione (GSH) and in the formation of protein-bound HNE in plasma membrane. In addition, HNE strongly induced intracellular peroxide production, suggesting that HNE e
Lipoprotein peroxidation, especially the modification of apolipoprotein B-100, has been implicated to play an important role in the pathogenesis of atherosclerosis. However, there have been few detailed insights into the chemical mechanism of derivatization of apolipoproteins during oxidation. In the present study, we provide evidence that the formation of the toxic pollutant acrolein (CH2=CH-CHO) and its conjugate with lysine residues is involved in the oxidative modification of human low densi
Cytotoxic action of membrane lipid peroxidation product 4-hydroxynonenal (HNE) is due mainly to its facile reactivity with proteins (Esterbauer, H., Schaur, R. J., and Zollner, H. (1991) Free Radical Biol. Med. 11, 77-80). In the present study, the detailed mechanism of HNE modification of a key enzyme in intermediary metabolism, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is studied mainly focusing on the formation of HNE-amino acid adducts in the enzyme. When GAPDH (1 mg/ml) was treated
We find that histidine residues in proteins are major targets for reaction with the lipid peroxidation product 4-hydroxynon-2-enal (HNE). Reaction of insulin (which contains no sulfhydryl groups) with HNE leads to the generation of HNE-protein adducts, which are converted to radioactive derivatives upon subsequent treatment with NaB[3H]H4. Amino acid analysis of the modified protein showed that the HNE treatment leads to the selective loss of histidine residues and the stiochiometric formation o
Methylglyoxal (MG), an endogenous metabolite that increases in diabetes and is a common intermediate in the Maillard reaction (glycation), reacts with proteins and forms advanced glycation end products. In the present study, we identify a novel MG-arginine adduct and also characterize the structure of a major fluorescent adduct. In addition, we describe the immunochemical study on the MG-arginine adducts using monoclonal antibody directed to MG-modified protein. Upon incubation of Nalpha-acetyl-
We report here the development of an immunochemical procedure that uses an antibody specific to the 4-hydroxynonenal (HNE) moiety for the detection of HNE-protein adducts. The HNE-specific antibody was prepared by immunizing rabbits with a HNE-keyhole limpet hemocyanin conjugate and purifying the rabbit serum on an affinity gel prepared by covalent attachment of a HNE-conjugated heptapeptide. When various preparations of glyceraldehyde-3-phosphate dehydrogenase containing 0-7.0 equivalent of HNE
It has been proposed that plasma low-density lipoprotein (LDL) undergoes oxidative modification before it can give rise to foam cells in atherosclerosis. Oxidation of LDL generates a variety of reactive aldehyde products including 4-hydroxy-2-nonenal (HNE), which may covalently attach to the LDL apolipoproteins. We here present direct evidence that HNE derivatization of LDL forms Michael addition-type adducts of HNE with histidine and lysine residues of apolipoprotein B-100 (apoB) and also demon
Inactivation of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) by its own reaction product H2O2 is a well-known phenomenon. Generation of the hydroxyl radical has been a matter of great concern, and the target molecule has been regarded as its own active site histidine residues, whose oxidized forms have not yet been identified (Hodgson, E.K., and Fridovich, I. (1975) Biochemistry 14, 5294-5299). Here we report on the identification of oxidized histidines generated at the active site of Cu,Zn-SOD by rea
In the present study, we find that cyclopentenone prostaglandins (PGs) of the J(2) series, naturally occurring derivatives of PGD(2), are potential inducers of intracellular oxidative stress that mediates cell degeneration. Based on an extensive screening of diverse chemical agents on induction of intracellular production of reactive oxygen species (ROS), we found that the cyclopentenone PGs, such as PGA(2), PGJ(2), Delta(12)-PGJ(2), and 15-deoxy-Delta(12,14)-PGJ(2), showed the most potent pro-o
