INCREASED LIPID PEROXIDATION IN PATIENTS WITH ACERULOPLASMINEMIA
| Project/Area Number |
08670702
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
MIYAJIMA Hiroaki HAMAMATSU UNIV.SCH.OF MED., FIRST DEPARTMENI OF MEDICINE,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (90221613)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Hideaki HAMAMATSU UNIV.SCH.OF MED., FIRST DEPARTMENI OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (70270981)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | CERULOPLASMIN / LIPID PEROXIDATION / IRON / VERY LONG-CHAIN FATTY ACID / PEROXISOME / FREE RADICAL / GENE MUTATION / IRON CHELATOR / セルロプラスミン欠損症 |
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| Research Abstract |
Aceruloplasminemia is a newly recognized autosomal recessive disorderof iron metabolism resulting in neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. Clinically it is recognized as a triad of diabetes, retinal degeneration and neurologic disease. This disease is characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, low serum iron concentration, and iron accumulation in the brain, liver, and other tissues. Iron is an important catalyst of oxyradical-mediated cellular and tissue injury. We report here on the identification of increased lipid peroxidation in the plasma and erythrocyte membranes of affected family members with aceruloplasminemia. Plasma lipid peroxidation was determined as thiobarbituric acid-reactive products (TBA products) in plasma samples from twenty controls, eight heterozygotes, and three homozygotes. The level of lipid peroxides was three times greater in homozygous patients and an inverse relation w
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as found between ceruloplasmin concentrations and quantitative estimates of TBA products (r=-0.9l5 : p<0.01). Profile of fatty acids in the erythrocyte membranes was examined by gas chromatography-mass spectrometry. We found accumulation of very-long-chain fatty acids, cis-17-hexacosenoic acid (C26 : 1) and hexacosanoic acid (C26 : 0), in the blood cells of aceruloplasminemia patients. The ratios of C26 : 1/C22 : 0 and C26 : 0/C22 : 0 were also elevated. In addition, a marked excess in the alpha-hydroxy fatty acids [alpha-hydroxydocosanoic acid (hC22 : 0), alpha-hydroxytricosanoic acid (hC23 : 0), alpha-hydroxytetracosanoic acid (hC24 : 0), and alpha-hydroxytetracosenoicacid (hC24 : 1)] was also detected in these cells. It is likely that free radicals generated in patients with aceruloplasminemia may interrupt the peroxisomal beta-oxidation of fatty acids, and may result in lipid hydrolysis during lipid peroxidation in the erythrocyte membrane. Taken together these data suggest that increased susceptibility to lipid peroxidation in plasma and the erythrocyte membrane may contribute to the unique neuropathology observed in patients with acerul oplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia. Less
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Report
(3 results)
Research Products
(15 results)
