Reduced expression of epidermal growth factor receptors in rat liver during aging

Amrita Kamat; Paramita M. Ghosh; Renee L. Glover; Bing Zhu; Chih Ko Yeh; Goutam Ghosh Choudhury; Michael S. Katz

doi:10.1093/gerona/63.7.683

Reduced expression of epidermal growth factor receptors in rat liver during aging

Amrita Kamat, Paramita M. Ghosh, Renee L. Glover, Bing Zhu, Chih Ko Yeh, Goutam Ghosh Choudhury, Michael S. Katz

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligandinduced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.

Original language	English (US)
Pages (from-to)	683-692
Number of pages	10
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	63
Issue number	7
DOIs	https://doi.org/10.1093/gerona/63.7.683
State	Published - Jul 2008

Keywords

Extracellular signal-regulated kinase
Hepatocytes
Receptor dimerization
Receptor tyrosine kinase

ASJC Scopus subject areas

General Medicine

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10.1093/gerona/63.7.683

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title = "Reduced expression of epidermal growth factor receptors in rat liver during aging",

abstract = "Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligandinduced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.",

keywords = "Extracellular signal-regulated kinase, Hepatocytes, Receptor dimerization, Receptor tyrosine kinase",

author = "Amrita Kamat and Ghosh, {Paramita M.} and Glover, {Renee L.} and Bing Zhu and Yeh, {Chih Ko} and Choudhury, {Goutam Ghosh} and Katz, {Michael S.}",

note = "Funding Information: ACKNOWLEDGMENTS This work was supported by a University Research Council Grant from The University of Texas Health Science Center at San Antonio (to A. Kamat), medical research funds from the Department of Veterans Affairs (to C.-K. Yeh, G. Ghosh Choudhury, and M.S. Katz), grants from the National Institutes of Health (RO1 DK 50190) and the Juvenile Diabetes Research Foundation (to G. Ghosh Choudhury), and a research grant from the Kronos Longevity Research Institute (to M. S. Katz). G. Ghosh Choudhury is a Research Career Scientist in the Department of Veteran Affairs.",

year = "2008",

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doi = "10.1093/gerona/63.7.683",

language = "English (US)",

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pages = "683--692",

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AU - Ghosh, Paramita M.

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AU - Zhu, Bing

AU - Yeh, Chih Ko

AU - Choudhury, Goutam Ghosh

AU - Katz, Michael S.

N1 - Funding Information: ACKNOWLEDGMENTS This work was supported by a University Research Council Grant from The University of Texas Health Science Center at San Antonio (to A. Kamat), medical research funds from the Department of Veterans Affairs (to C.-K. Yeh, G. Ghosh Choudhury, and M.S. Katz), grants from the National Institutes of Health (RO1 DK 50190) and the Juvenile Diabetes Research Foundation (to G. Ghosh Choudhury), and a research grant from the Kronos Longevity Research Institute (to M. S. Katz). G. Ghosh Choudhury is a Research Career Scientist in the Department of Veteran Affairs.

PY - 2008/7

Y1 - 2008/7

N2 - Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligandinduced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.

AB - Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligandinduced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.

KW - Extracellular signal-regulated kinase

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Reduced expression of epidermal growth factor receptors in rat liver during aging

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