Lin S, Li X, Yan G
Department of Pediatrics, Fist Affiliated Hospital, Department of Pharmacology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510080.
Zhonghua Yi Xue Za Zhi. 1999 Feb;79(2):125-8.
To investigate the mechanism of bilirubin-induced neurotoxicity from cellular and molecular level.
Bilirubin was exposed to primary cultured rat cerebellar granule and cortical neurons and its neurotoxicity was observed DNA staining and agars gel electrophores were used to identify the biochemical and morphological features of bilirubin-induced neurotoxicity in cultured cerebellar granule and cortical neurons.
Bilirubin selectively induced death of cerebellar granule neurons in a concentration- and time-dependent manner. Neuronal death displayed biochemical and morphological features of apoptotic nuclei: condensation of nuclear chromatin and DNA fragmentation. RNA and protein synthesis inhibitors blocked the neurotoxicity induced by bilirubin. However, the cortical neurons displayed a relative insensitivity to bilirubin.
Bilirubin induced neuron death is an active process, requiring de novo synthesis of RNA and protein. Bilirubin may selectively induce apoptosis of cerebellar granule neurons.
从细胞和分子水平研究胆红素诱导神经毒性的机制。
将胆红素作用于原代培养的大鼠小脑颗粒神经元和皮层神经元,通过DNA染色观察其神经毒性,采用琼脂糖凝胶电泳鉴定胆红素诱导培养的小脑颗粒神经元和皮层神经元神经毒性的生化和形态学特征。
胆红素以浓度和时间依赖性方式选择性诱导小脑颗粒神经元死亡。神经元死亡表现出凋亡细胞核的生化和形态学特征:核染色质凝聚和DNA片段化。RNA和蛋白质合成抑制剂可阻断胆红素诱导的神经毒性。然而,皮层神经元对胆红素表现出相对不敏感。
胆红素诱导的神经元死亡是一个活跃过程,需要RNA和蛋白质的从头合成。胆红素可能选择性诱导小脑颗粒神经元凋亡。