Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Isoprenoids and astroglial cell cycling: Diminished mevalonate availability and inhibition of dolichol‐linked glycoprotein synthesis arrest cycling through distinct mechanisms

Isoprenoids and astroglial cell cycling: Diminished mevalonate availability and inhibition of... 10.1002/jcp.1041490215.abs Primary astroglial cultures were used to compare the relationships to cell cycling of dolichol‐linked glycoprotein synthesis, and of availability of mevalonate, the precursor of dolichol and other isoprenoid lipids. With shift‐up to 10% serum (time 0) after 48 h of serum depletion, the proportion of cells in S phase (bromodeoxyuridine immunofluorescence) remained under 15% for 12 h, then increased by 20 h to 72 ± 10%; DNA synthetic rates (thymidine incorporation) increased 5‐fold. S phase transition was prevented by addition at 10–12 h of tunicamycin, an inhibitor of transfer of saccharide moieties to dolichol. Mevinolin, an inhibitor of mevalonate biosynthesis, also blocked cycle progression when added at this time. However, mevinolin markedly inhibited the isoprenoid pathway, as reflected by over 90% reduction of sterol synthesis, without inhibiting net glycoprotein synthesis. Removal of mevinolin after a 24 h exposure delayed S phase until 48 h, following recovery of sterol synthesis, even though kinetics of glycoprotein synthesis were unaffected. Tunicamycin removal after 24 h spared sterol synthesis, but caused delay of S phase until 72 h, following recovery of glycoprotein synthesis. In mevinolin‐treated cultures, S phase transition was restored by 1 h of exposure to mevalonate at 10 h, although cycling was thereby rendered sensitive to inhibition by cycloheximide and by tunicamycin. Cell cycle progression following hydroxyurea exposure and release was unaffected by mevinolin, tunicamycin, or cycloheximide. Thus, in these developing astroglia, mevalonate and its isoprenoid derivatives have at least two cell cycle‐specific roles: dolichol‐linked glycoprotein synthesis is required at or before the G1/S transition, while a distinct mevalonate requirement is apparent also in late G1. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

Isoprenoids and astroglial cell cycling: Diminished mevalonate availability and inhibition of dolichol‐linked glycoprotein synthesis arrest cycling through distinct mechanisms

Download PDF
9 pages

Loading next page...
 
/lp/wiley/isoprenoids-and-astroglial-cell-cycling-diminished-mevalonate-si64XKf6ga

References (55)

Publisher
Wiley
Copyright
Copyright © 1991 Wiley‐Liss, Inc.
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/jcp.1041490215
pmid
1748720
Publisher site
See Article on Publisher Site

Abstract

10.1002/jcp.1041490215.abs Primary astroglial cultures were used to compare the relationships to cell cycling of dolichol‐linked glycoprotein synthesis, and of availability of mevalonate, the precursor of dolichol and other isoprenoid lipids. With shift‐up to 10% serum (time 0) after 48 h of serum depletion, the proportion of cells in S phase (bromodeoxyuridine immunofluorescence) remained under 15% for 12 h, then increased by 20 h to 72 ± 10%; DNA synthetic rates (thymidine incorporation) increased 5‐fold. S phase transition was prevented by addition at 10–12 h of tunicamycin, an inhibitor of transfer of saccharide moieties to dolichol. Mevinolin, an inhibitor of mevalonate biosynthesis, also blocked cycle progression when added at this time. However, mevinolin markedly inhibited the isoprenoid pathway, as reflected by over 90% reduction of sterol synthesis, without inhibiting net glycoprotein synthesis. Removal of mevinolin after a 24 h exposure delayed S phase until 48 h, following recovery of sterol synthesis, even though kinetics of glycoprotein synthesis were unaffected. Tunicamycin removal after 24 h spared sterol synthesis, but caused delay of S phase until 72 h, following recovery of glycoprotein synthesis. In mevinolin‐treated cultures, S phase transition was restored by 1 h of exposure to mevalonate at 10 h, although cycling was thereby rendered sensitive to inhibition by cycloheximide and by tunicamycin. Cell cycle progression following hydroxyurea exposure and release was unaffected by mevinolin, tunicamycin, or cycloheximide. Thus, in these developing astroglia, mevalonate and its isoprenoid derivatives have at least two cell cycle‐specific roles: dolichol‐linked glycoprotein synthesis is required at or before the G1/S transition, while a distinct mevalonate requirement is apparent also in late G1.

Journal

Journal of Cellular Physiology – Wiley

Published: Nov 1, 1991

There are no references for this article.