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Neuron dysfunction in bilirubin-induced apoptosis causes kernicterus

胆红素诱导的细胞凋亡中的神经元功能障碍导致核黄疸

基本信息

批准号：
10671018
负责人：
YAMAGUCHI Tokio
金额：
$ 1.54万
依托单位：
Tokyo Medical and Dental University, Medical Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671018/
关键词：
bilirubin kernicterus apoptosis neuron biliverdin urobilin stercobilin mitochondria

项目摘要

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.

新生儿黄疸仍然是一个常见的问题。核黄疸，虽然罕见，仍然是一个非常真实的关注的全职和早产儿。这种神经系统综合征与基底神经节、某些脑干核团和浦肯野细胞中的选择性神经元脆弱性有关。然而，胆红素损伤神经元的机制仍不清楚。在这些研究中，我们发现胆红素导致核黄疸在胆红素诱导的细胞凋亡。在原代培养的神经元中，胆红素（30μg/ml）在含10%小牛血清白蛋白的DMEM培养基中以凋亡方式而非坏死方式对神经元（CGC：Cerebral Granular Cells）造成完全损伤。令我们惊讶的是，尽管浓度较低（3μg/ml），胆绿素并没有改变神经元（CGC）的活力。而尿胆素和粪胆素在低浓度（30μg/ml）下均未显示毒性。而在胆红素和Ca ~（2+）D_12 + Ca ~（2+）D_1离子（CaSO_4 ~（2+）D_2）共同作用下，神经元不发生凋亡。其次，我们研究了胆红素在细胞内神经元的分布。有趣的是，胆红素定位于神经元细胞器中的线粒体。