2002 Fiscal Year Final Research Report Summary
Mitochondria injuries of Peritoneal Mesothelial Cells induced by oxidative stress
| Project/Area Number |
13671131
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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 |
Kidney internal medicine
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
SASAKI Tamaki Kawasaki Medical School Medicine Associate Professor, 医学部, 助教授 (30187124)
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| Co-Investigator(Kenkyū-buntansha) |
SHINDO Akihisa Kawasaki Medical School Medicine Assistant Professor, 医学部, 講師 (00278920)
KASHIHARA Naoki Kawasaki Medical School Medicine Professor, 医学部, 教授 (10233701)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Peritoneum / Mesothelial cell / Oxidative stress / Mitochondria / Angiogenesis / Klotho mouse |
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| Research Abstract |
Oxidative stress by reactive oxygen species (ROS) is thought to be involved in the pathogenesis of various diseases. The pathological effect of oxidative stress on the peritoneum was studied basically with 8- OHdG. Immunohistochemical staining of 8- OHdG was weakly detected in the mesothelial cells of the healthy control, whereas strong staining was observed in the mesothelial cells and vascular walls of patients with sclerosing peritonitis. The presence of 8- OHdG in infiltrative cells in peritonitis was confirmed. The 8- OHdG levels in CAPD solution increased in proportion to the duration of dialysis irrespective of age, and they were high in the patients with peritonitis. Thereforem the 8- OHdG level in CAPD solutions might possibly be used as a clinical marker of inflammttion of the peritoneum and impairment of mesothelial cells
Subsequently, the effect of a high glucose concentration (HG group, 214mM) on rat culture mesothelial cells was investigated. The ROS production was visuali
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zed and checked by Dichlorofluorescein diacetat. Upon exposure to HG, the mesothelial cells produced more ROS than those of the control group. These results suggest that the mitochondria were extremely vulnerable to oxidative stress because they were a major intracellular source of ROS
Next, neoangiogenesis during acute peritonitis was investigated morphologically. Fluorescent Griffonia simplicifolia 1 lectin was used to visualize the pattern of capillaries in the peritoneum by laser scanning confocal microscopy. Branching anastomoses between the parallel parent capillaries formed an irregular lace- like meshwork rather than individual straight interconnections. In the peritonitis model rats, cell infiltration was recognized on the surface of the peritoneum, and some of these cells expressed CD34. Immunohistocemistry revealed expression of Flk-1, Flt-1, and Tie-2 in these cells. These results may represent a new and promising strategy for dealing with peritoneal dysfunction by clinical application to new vessel formation Less
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