Linked Life Data

15888087

Source:http://linkedlifedata.com/resource/pubmed/id/15888087

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-5-12
pubmed:abstractText
The intracellular protozoan Toxoplasma gondii lacks a de novo mechanism for cholesterol synthesis and therefore must scavenge this essential lipid from the host environment. In this study, we demonstrated that T. gondii diverts cholesterol from low-density lipoproteins for cholesteryl ester synthesis and storage in lipid bodies. We identified and characterized two isoforms of acyl-CoA:cholesterol acyltransferase (ACAT)-related enzymes, designated TgACAT1alpha and TgACAT1beta in T. gondii. Both proteins are coexpressed in the parasite, localized to the endoplasmic reticulum and participate in cholesteryl ester synthesis. In contrast to mammalian ACAT, TgACAT1alpha and TgACAT1beta preferentially incorporate palmitate into cholesteryl esters and present a broad sterol substrate affinity. Mammalian ACAT-deficient cells transfected with either TgACAT1alpha or TgACAT1beta are restored in their capability of cholesterol esterification. TgACAT1alpha produces steryl esters and forms lipid bodies after transformation in a Saccharomyces cerevisiae mutant strain lacking neutral lipids. In addition to their role as ACAT substrates, host fatty acids and low-density lipoproteins directly serve as Toxoplasma ACAT activators by stimulating cholesteryl ester synthesis and lipid droplet biogenesis. Free fatty acids significantly increase TgACAT1alpha mRNA levels. Selected cholesterol esterification inhibitors impair parasite growth by rapid disruption of plasma membrane. Altogether, these studies indicate that host lipids govern neutral lipid synthesis in Toxoplasma and that interference with mechanisms of host lipid storage is detrimental to parasite survival in mammalian cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1462-5814
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
849-67
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15888087-Amino Acid Sequence, pubmed-meshheading:15888087-Animals, pubmed-meshheading:15888087-Binding Sites, pubmed-meshheading:15888087-Cell Membrane, pubmed-meshheading:15888087-Cells, Cultured, pubmed-meshheading:15888087-Cholesterol Esters, pubmed-meshheading:15888087-Cricetinae, pubmed-meshheading:15888087-Cricetulus, pubmed-meshheading:15888087-Endoplasmic Reticulum, pubmed-meshheading:15888087-Humans, pubmed-meshheading:15888087-Isoenzymes, pubmed-meshheading:15888087-Lipids, pubmed-meshheading:15888087-Mice, pubmed-meshheading:15888087-Microscopy, Immunoelectron, pubmed-meshheading:15888087-Molecular Sequence Data, pubmed-meshheading:15888087-Mutation, pubmed-meshheading:15888087-Palmitates, pubmed-meshheading:15888087-Saccharomyces cerevisiae, pubmed-meshheading:15888087-Sterol O-Acyltransferase, pubmed-meshheading:15888087-Toxoplasma
pubmed:year
2005
pubmed:articleTitle
Host cell lipids control cholesteryl ester synthesis and storage in intracellular Toxoplasma.
pubmed:affiliation
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural