Effects of Cell Proliferation and Cell Death on the Expression of Sunescence Marker Protein-30 (SMP30) in the Rat Liver.

细胞增殖和细胞死亡对大鼠肝脏中太阳光标记蛋白 30 (SMP30) 表达的影响。

基本信息

批准号：
06833018
负责人：
FUJITA Toshiko
金额：
$ 1.34万
依托单位：
Tokyo Metropolitan Institute of Gerontology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

We reported a novel liver protein, the amounts of which decreased androgen-independently with aging.We designated this protein as senescence marker protein-30 (SMP30) .We have isolated rat and hunan cDNA clones encoding SMP30.SMP30 is a calcium binding protein also called regucalcin which plays a role in the regulation of various enzymes by regulating calcium ions in hepatocytes.It was suggested that the decrease of SMP30 with aging may lead to senile changes in the calcium signaling system of aged livers.The amount of SMP30 in the liver was relatively large (2%) and the deduced amino acid sequence of human SMP30 showed a remarkable homology with that of rat SMP30(89% similarity).The results of genomic Southerm hybridization also indicated the strong evolutionary conservation of SMP30 gene among higher animals.These results support the potentially critical role of SMP30 in tissue specific biological functions of the liver and kidney.SMP30 is exclusively expressed in hepatocytes and renal proximal tubular epitheliums, both of which show high activity of metabolism and transportation.In this study, to elucidate the physiological function of SMP30, we repout the examination of the SMP30 expression in the compensatory hepatocyte proliferation and direct hyperplasia after treatments of two different types of stimulants.Both experimental conditions involve in vivo inductions of liver cell proliferation and liver cell death.SMP30 was isduced by both of proliferative stimuli.However, these inductions were not correlated with DNA synthesis nor mitosis.These results implies that SMP30 is up-regulated in hepatocytes after the proliferative stimuli, but not associated with DNA synthesis and mitosis.Next, we examined the effect of phenobarbital which is a very strong inducers of detoxifying system enzymes.The results suggest that SMP30 is not involved in phase-I enzymes of the drug metabolic system.

我们报道了一种新的肝脏蛋白，其数量随衰老而减少，与雄激素无关。我们将这种蛋白命名为衰老标记蛋白-30 (SMP30)。我们分离了编码 SMP30 的大鼠和湖南 cDNA 克隆。SMP30 也是一种钙结合蛋白称为reguccalcin，通过调节肝细胞内的钙离子，发挥多种酶的调节作用。有人提出，SMP30随着衰老而减少，可能导致老年性改变肝脏中SMP30的含量较多（2%），推导的人SMP30氨基酸序列与大鼠SMP30的氨基酸序列具有显着的同源性（89%相似性）。基因组Southern杂交也表明SMP30基因在高等动物中具有很强的进化保守性。这些结果支持SMP30在肝脏和肾脏的组织特异性生物学功能中潜在的关键作用。SMP30仅在肝细胞和肾近端肾小管上皮均表现出较高的代谢和运输活性。本研究为了阐明SMP30的生理功能，我们对两种药物治疗后肝细胞代偿性增殖和直接增生中SMP30的表达进行了检测。不同类型的兴奋剂。两种实验条件均涉及体内诱导肝细胞增殖和肝细胞死亡。SMP30是由两种增殖诱导的然而，这些诱导与 DNA 合成和有丝分裂无关。这些结果表明，SMP30 在增殖刺激后在肝细胞中上调，但与 DNA 合成和有丝分裂无关。接下来，我们检查了苯巴比妥的作用，苯巴比妥是一种非常强的解毒系统酶诱导剂。结果表明，SMP30 不参与药物代谢系统的 I 相酶。