Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes. 1998

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

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004256 DNA Polymerase I A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. DNA Polymerase alpha,DNA-Dependent DNA Polymerase I,Klenow Fragment,DNA Pol I,DNA Dependent DNA Polymerase I,Polymerase alpha, DNA
D004259 DNA-Directed DNA Polymerase DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair. DNA Polymerase,DNA Polymerases,DNA-Dependent DNA Polymerases,DNA Polymerase N3,DNA Dependent DNA Polymerases,DNA Directed DNA Polymerase,DNA Polymerase, DNA-Directed,DNA Polymerases, DNA-Dependent,Polymerase N3, DNA,Polymerase, DNA,Polymerase, DNA-Directed DNA,Polymerases, DNA,Polymerases, DNA-Dependent DNA
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004272 DNA, Mitochondrial Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins. Mitochondrial DNA,mtDNA
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D000074002 DNA Polymerase gamma A DNA-directed DNA polymerase that functions in the replication of MITOCHONDRIAL DNA. Mutations in the gene that encodes this enzyme (POLG) are associated with some forms of OPHTHALMOPLEGIA, CHRONIC EXTERNAL PROGRESSIVE. DNA Polymerase Subunit gamma-1,PolG-alpha,Mitochondrial DNA Polymerase,DNA Polymerase Subunit gamma 1,DNA Polymerase, Mitochondrial,PolG alpha,Polymerase gamma, DNA,Polymerase, Mitochondrial DNA

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