衰老对大鼠肝细胞中表皮生长因子刺激的特定基因复制的影响。

Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes.

作者信息

Kitano S, Bohr V A, Reed T D, Haggerty C M, May A, Roth G S

机构信息

Molecular Physiology and Genetics Section, Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21224, USA.

出版信息

J Cell Physiol. 1998 Jul;176(1):32-9. doi: 10.1002/(SICI)1097-4652(199807)176:1<32::AID-JCP4>3.0.CO;2-9.

DOI:10.1002/(SICI)1097-4652(199807)176:1<32::AID-JCP4>3.0.CO;2-9

PMID:9618142

Abstract

EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway.

摘要

在来自成熟（6个月）和衰老（24个月）大鼠的原代肝细胞培养物中，检测了表皮生长因子（EGF）刺激的特定基因复制情况。还评估了基础状态和EGF刺激下的[³H]胸苷掺入量、DNA聚合酶α活性以及总细胞DNA。所检测的基因包括二氢叶酸还原酶（DHFR）、c-myc以及总线粒体DNA（mt DNA）。尽管随着年龄增长，EGF刺激的[³H]胸苷掺入量、DNA聚合酶α活性、总细胞DNA、DHFR和c-myc基因特异性DNA复制均有所降低，但mt DNA复制不受EGF或年龄的影响。染色体DNA复制主要由DNA聚合酶α介导，而mt DNA复制由其自身的DNA聚合酶γ介导。因此，与年龄相关的受刺激DNA复制下降似乎主要与DNA聚合酶α激活途径有关。