THE EXPERIMENTAL RESEARCH FOR DEVELOPMENT OF GENE-AND DRUG-THERAPY FOR NEONATAL HYPERBILIRUBINEMIA

新生儿高胆红素血症基因和药物治疗开发的实验研究

• 批准号: 08670935
• 负责人: KEINO Hiroomi
• 金额: $ 1.47万
• 依托单位: PEDIATRICS
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670935/
• 关键词: BILIRUBIN; GEN-THERAPY; GLUCURONOSYLTRANSFERASE; PROTOPORPHYRIN; PROTEOGLYCAN; OLIGOSACCARIDE; CEREBERUM; PURKINJE CELL; ビリルビン; プルキンエ細胞; 糖タンパク質; ポルフィリン; neuroglycan C; レクチン; リソソーム; ラジカル; キトオリゴ糖; キトサン; ヘパランサルフェイト; ペントサン

We re-analyzed the genetic background of patients with Gilbert's syndrome. A new kind of point mutation and decrease of frequency of TATA repeat were investigated in regulation site and five kinds of mutations were also recognized in the exons of bilirubin UGT gene. Almost all patients with Gilbert's syndrome had two mutations.The combination of injection of tin-projoporphyrin (SnPP) and photoirradiaiton reacted with neurological signs. Intra-ventral injection of SnPP showed soon and irritable neurological signs. Lysosomes prepared from suckling rat brain showed the release of arylsulfatase under lower condition of SnPP (under 10 nM).It is known that day 7 is the most critical for cerebellar hypoplasia in rats due to bilirubin. Cerebella of postnatal day 7 rats were rich in glycoproteins.Purkinje cells may be rich in N-linked oligosaccharides, with terminal sugar structures that resemble blood-group-related antigens (type H). Neuroglycan C, a new neuron specific condroitinesulfate proteoglycan, immunolocalized to the soma (P7) and the thick stems (adult), not the thin branches, of the Purkinje cells.. This finding suggests the involvement of glycoproteins in the differential adhesion of the climbing and parallel fibers with the Purkinje cell dendrites.

我们重新分析了吉尔伯特综合征患者的遗传背景。在胆红素UGT基因的调控位点发现了一种新的点突变和TATA重复频率的降低，并在其外显子中发现了5种突变。几乎所有吉尔伯特综合症患者都有两种突变。注射锡-投影卟啉（SnPP）与光照射联合使用可改善神经系统症状。腹侧注射SnPP后出现快速、易激的神经学症状。乳大鼠脑溶酶体在较低SnPP条件下（10 nM以下）有芳基磺化酶的释放。众所周知，由于胆红素的作用，第7天是大鼠小脑发育不全的关键。出生后第7天的大鼠小脑中富含糖蛋白。浦肯野细胞可能富含n -连接寡糖，其末端糖结构类似于血型相关抗原（H型）。Neuroglycan C是一种新的神经元特异性硫酸包络素蛋白多糖，免疫定位于浦肯野细胞的体细胞（P7）和粗茎（成体），而不是细分枝。这一发现表明糖蛋白参与了攀爬纤维和平行纤维与浦肯野细胞树突的不同粘附。

项目成果

E.Watanabe, F.Matsui, H.Keino, K.Ono, Y.Kushima, M.Noda, A.Oohira: "A membrane-bound heparan sulfate proteoglycan that is transiently expressed on growitg axons in the rat brain." Journal of Neuroscience Research. 44. 84-96 (1996)

E.Watanabe、F.Matsui、H.Keino、K.Ono、Y.Kushima、M.Noda、A.Oohira：“一种膜结合的硫酸乙酰肝素蛋白聚糖，在大鼠大脑的生长轴突上瞬时表达。”

Fukui,K.: "Experimental creation of susiform carotid artery aneurysms using vein" Neurosurgery. 43. 1419-1426 (1998)

Fukui,K.：“利用静脉实验性制作镰状颈动脉瘤”神经外科。

E.Watanabe: "Amembrane-bound heparan sulfate proteoglycan that is transiently expressed axons in the rat brain." Journal of Neuroscience Research. 44. 84-96 (1996)

E.Watanabe：“膜结合的硫酸乙酰肝素蛋白多糖在大鼠大脑中瞬时表达轴突。”

H.Keino et al.: "Tin-protoporphyrin plus photo-irradiation induces a release of arylsulfatase from lysosomes of rat hepatocytes in vitro and in vivo" Biomedical Research. 17. 231-235 (1996)

H.Keino 等人：“锡原卟啉加上光照射可诱导体外和体内大鼠肝细胞溶酶体释放芳基硫酸酯酶”生物医学研究。