2005 Fiscal Year Final Research Report Summary
Potential contribution of oxidative stress and oxidized phosphatidylcholine to nonalcoholic steatohepatitis.
| Project/Area Number |
16590287
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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 |
Human pathology
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| Research Institution | Osaka City University |
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Principal Investigator |
IKURA Yoshihiro Osaka City University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究科, 講師 (00240953)
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| Project Period (FY) |
2004 – 2005
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| Keywords | nonalcoholic steatohepatitis / oxidative stress / lipid peroxide / oxidized phosphatidylcholine / scavenger receptor |
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| Research Abstract |
Human liver samples from patients with fatty liver disorders including nonalcoholic steatohepatitis (NASH) and chronic hepatitis C obtained at autopsy or by biopsy was analyzed by following immunohistochemical examinations.
Localization of oxidized phosphatidylcholine (oxPC) in livers of NASH was assumed to indicate oxidative injury. The oxPC localization was often observed in hepatocytes with fat degeneration and in apoptotic hepatocytes, suggesting a close relation with the oxidative injury. Besides a strong oxidative enzyme, neutrophil myeloperoxidase, vasoactive agents considered highly probable as the source of the oxidative stress, and thus, expressions of angiotensin II type 1 receptor and endothelin system in the diseased livers were studied. The results elucidated its relation to liver pathology, especially to hepatic fibrosis (Hepatol Res. 2005 ; J Pathol. 2004).
Next, immunoelectron microscopic observation of NASH livers was done, and oxPC immunoreactivity was seen at membrano
… More
us structures of lipid droplets and degenerated hepatocytes, which probably implied oxidative injury. Endoplasmic reticulum and mitochondria in the oxPC-positive hepatocyte were markedly dilated. A close localization of these oxPC-positive hepatocytes and myeloperoxidase-positive neutrophils was observed and suggested a role for neutrophils in generation of oxidative stress in liver tissues of NASH.
Concerning to oxPC processing, its receptor expression was investigated. Scavenger receptors, such as SR-B1 and CD36, correspond to the oxPC receptor. Their expressions in NASH livers were seen in Kupffer cells as well as activated stellate cells, suggesting active contribution of the ligand-receptor interaction to hepatic fibrosis.
These findings together were systematically interpreted and organized into one concept, which was published in the specialized journal (Hepatology. 2006 ; Hepatology. 2005).
On the other hand, SR-B1 expression in livers of hepatitis C was correlated to the viral load in the affected liver tissues. SR-B1 may promote internalization of hepatitis C virus in hepatocytes. This concept has been supported by recent experimental investigations. These evidence and concept were united and published as a short report (J Clin Virol. 2005 ; Hepatology. 2004). Less
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