Project/Area Number |
10671018
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Embryonic/Neonatal medicine
|
Research Institution | Tokyo Medical and Dental University, Medical Research Institute |
Principal Investigator |
YAMAGUCHI Tokio Tokyo Med. & Dent. Univ., Medical. Res. Inst., Associate Prof., 難治疾患研究所, 助教授 (30134745)
|
Co-Investigator(Kenkyū-buntansha) |
ASAKA Rei Tokyo Med. & Dent. Univ., Medical. Res. Inst., Res. Assistant, 難治疾患研究所, 助手 (20167224)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | bilirubin / kernicterus / apoptosis / neuron / biliverdin / urobilin / stercobilin / mitochondria |
Research Abstract |
Neonatal jaundice continues to acommon problem. Kernicterus, although rare, continues to be a very real concern in both full-time and preterm infants. This neurologic syndrome has been associated with selective neuronal vulnerability in the basal ganglia, certain brainstem nuclei, and Purkinje cells. However, the mechanism by which bilirubin damages neurons remains unclear. In these studies, we found that bilirubin caused kernicterus in bilirubin-induced apoptosis. In primary cultured neuron, bilirubin (30μg/ml) completely damaged neuron (CGC : Cerebral Granular Cells) by the mechanism of apoptosis style, but not necrosis style in the DMEM containing 10% calf serum albmin. To ours surprise, biliverdin in spite of the low concentration (3μg/ml) did not change the viability of neurons (CGC). On the other side, urobilin and stercobilin did not show the toxicity regardless of the low concentration (30μg/ml) at all. However, if there are in both bilrubin and CaィイD12+ィエD1ion (CaSOィイD24ィエD2), neurons did not undergone apoptosis. Secondly, we have examined the distribution of bilirubin in intracellular neuron. Interestingly, bilirubin was localized in mitochondria among intracellular organelle of neurons.
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