Document Detail


Perillyl alcohol inhibits TCR-mediated [Ca(2+)](i) signaling, alters cell shape and motility, and induces apoptosis in T lymphocytes.
MedLine Citation:
PMID:  10805968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Perillyl alcohol (POH) inhibits isoprenylation and has shown anticancer and chemopreventive properties in rodent models. The mechanism that underlies the anticancer activity of POH and other isoprenylation inhibitors is unknown but has been postulated to involve decreased levels of isoprenylated Ras and Ras-related proteins. Previously we demonstrated that POH effectively inhibits human T cell proliferation in vitro and can prevent acute and chronic rejection in a rat cardiac transplant model. In this report, we investigate the effects of POH on T lymphocytes at the single-cell level. POH disrupts the polarized shape and motility of antigen-specific murine 1E5 T cells. Using an optical trap to position anti-CD3-coated beads in contact with 1E5 T cells, we demonstrate that POH inhibits their TCR-mediated calcium response. Furthermore, we show that POH preferentially induces apoptosis in PHA-activated human T cells as well as in 1E5 T cells.
Authors:
X Wei; M S Si; D K Imagawa; P Ji; B J Tromberg; M D Cahalan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular immunology     Volume:  201     ISSN:  0008-8749     ISO Abbreviation:  Cell. Immunol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-07-06     Completed Date:  2000-07-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6-13     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Affiliation:
Department of Physiology and Biophysics, University of California, Irvine, California, 92697, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Alkyl and Aryl Transferases / antagonists & inhibitors*
Animals
Apoptosis / drug effects*
Calcium / metabolism*
Cell Movement / drug effects*
Cell Polarity / drug effects
Cell Size / drug effects
Enzyme Inhibitors / pharmacology*
Humans
Mice
Monoterpenes*
Receptors, Antigen, T-Cell / metabolism*
Signal Transduction / physiology*
T-Lymphocytes / drug effects*,  metabolism,  physiology
Terpenes / pharmacology*
Grant Support
ID/Acronym/Agency:
GM41514/GM/NIGMS NIH HHS; RR01192/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Monoterpenes; 0/Receptors, Antigen, T-Cell; 0/Terpenes; 536-59-4/perilla alcohol; 7440-70-2/Calcium; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/geranylgeranyltransferase type-I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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