Effects of aging and calorie restriction of Fischer 344 rats on hepatocellular response to proliferative signals
| Autor: | Myriam Gorospe, Shizuo Ikeyama, Xiantao Wang, Nikki J. Holbrook, Gertrude C. Kokkonen, Jennifer L. Martindale |
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| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Male medicine.medical_specialty Aging Calorie restriction Blotting Western Cell Cycle Proteins Biology medicine.disease_cause Biochemistry Immediate-Early Proteins Endocrinology Genes jun Epidermal growth factor Internal medicine Protein Phosphatase 1 Genetics medicine Dietary Carbohydrates Phosphoprotein Phosphatases Animals RNA Messenger Phosphorylation Receptor Molecular Biology Cells Cultured Epidermal Growth Factor Cell growth Kinase Dual Specificity Phosphatase 1 Cell Biology DNA Hydrogen Peroxide Blotting Northern Precipitin Tests Rats Inbred F344 Stimulation Chemical Rats ErbB Receptors Hepatocytes Mitogen-Activated Protein Kinases Protein Tyrosine Phosphatases Oxidative stress Cell Division |
| Zdroj: | Experimental gerontology. 38(4) |
| ISSN: | 0531-5565 |
| Popis: | It is well established that the proliferative potential of the liver declines with aging. Epidermal growth factor (EGF)-stimulated DNA synthesis is reduced in hepatocytes from aged rats relative to young rats, and this reduction correlates with diminished activation of the extracellular signal-regulated kinase (ERK) pathway and lower phosphorylation of the EGF receptor on residue Y1173. Calorie restriction (CR) can increase rodent life span and retard many age-associated declines in physiologic function, but its influence on cell proliferation is unknown. Here, we investigated the effects of long-term CR on proliferation of hepatocytes derived from young and aged rats following in vitro stimulation with either low-dose hydrogen peroxide or EGF. CR reduced the proliferative response of hepatocytes derived from young hosts, but long-term CR was associated with enhanced proliferation in aged cells relative to that of ad libitum (AL)-fed animals. ERK activation mirrored the effects of CR on proliferation, in that young CR cells exhibited lower ERK activation than young AL cells, but old CR cells showed higher ERK activation than old AL cells. Finally, a decline in EGF receptor phosphorylation on Y1173, which normally occurs with aging, was absent in cells of old hosts maintained on long-term CR, supporting the view that alterations in this early signaling event underlie the age-related decline in proliferative potential in rat hepatocytes. |
| Databáze: | OpenAIRE |
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