Metabolism of Heparan Sulfate Proteoglycan in Rat Hepatocyte Cell Line and Its Role for Regulation of Cell Growth
Ishihara, Masayuki
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/70569
Description
Title
Metabolism of Heparan Sulfate Proteoglycan in Rat Hepatocyte Cell Line and Its Role for Regulation of Cell Growth
Author(s)
Ishihara, Masayuki
Issue Date
1988
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Abstract
A rat hepatocyte cell line which accumulates free heparan sulfate (HS) chains in the nucleus was labeled with $\sp{35}$SO$\sb4\sp{2-}$ and the rate of appearance of ($\sp{35}$SO$\sb4$) HS in the nucleus was measured. ($\sp{35}$SO$\sb4$) HS began to accumulate in the nucleus 2 h after the addition of $\sp{35}$SO$\sb4\sp{2-}$ and reached a steady state level after 20 h. HS was lost from the nuclei of pre-labeled cells with a t$\sb{1/2}$ of 8 h. At both 37$\sp\circ$C and 16$\sp\circ$C exogenous ($\sp{35}$SO$\sb4$) heparan sulfate proteoglycan (HSPG) was taken up by the cells and converted to free chains and about 10 percent of the internalized HS was transported into nucleus.
The core protein of newly secreted HSPG appears in the cell matrix covalently linked to a phosphatidylinositol moiety on plasma membrane which is then cleaved by a plasma membrane phospholipase C. The released HSPG becomes found to a inositol-PO$\sb4$ (IP)-specific receptor and is internalized and a portion of it is processed by a non-lysosomal pathway before delivery to the nucleus. Insulin activates the activity of the plasma membrane phospholipase C.
The level of nuclear HS is inversely prop. to the cell doubling time and, when growing cells reach confluence, increases 3-fold as the HS undergoes a change in structure. Culture conditions which lower the nuclear HS lower the rate of cell division in growing cells and cause confluent cells to lose contact inhibition. A cell surface HSPG released by treatment of the cells with IP, which is internalized very efficiently by cells and a portion of the internalized HSPG is processed and delivered to the nuclei, from confluent but not growing cultures causes cessation of cell division in logarithmically growing cells for approximately one cell cycle. In contrast, HSPG from growing cells but not from confluent cells stimulates the rate of cell division in growing cells. The dynamic metabolism of HS in hepatocyte and its correlations with cell growth suggest HS plays some role for the regulation of cell growth.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
