Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-17
pubmed:abstractText
Comparative Gene Identification-58 (CGI-58) is a member of the alpha/beta-hydrolase family of proteins. Mutations in the human CGI-58 gene are associated with Chanarin-Dorfman syndrome, a rare autosomal recessive genetic disease in which excessive triglyceride (TG) accumulation occurs in multiple tissues. In this study, we investigated the role of CGI-58 in cellular lipid metabolism in several cell models and discovered a role for CGI-58 in promoting the packaging of cytoplasmic TG into secreted lipoprotein particles in hepatoma cells. Using both gain-of-function and loss-of-function approaches, we demonstrate that CGI-58 facilitates the depletion of cellular TG stores without altering cellular cholesterol or phospholipid accumulation. This depletion of cellular TG is attributable solely to augmented hydrolysis, whereas TG synthesis was not affected by CGI-58. Furthermore, CGI-58-mediated TG hydrolysis can be completely inhibited by the known lipase inhibitors diethylumbelliferyl phosphate and diethyl-p-nitrophenyl phosphate, but not by p-chloro-mercuribenzoate. Intriguingly, CGI-58-driven TG hydrolysis was coupled to increases in both fatty acid oxidation and secretion of TG. Collectively, this study reveals a role for CGI-58 in coupling lipolytic degradation of cytoplasmic TG to oxidation and packaging into TG-rich lipoproteins for secretion in hepatoma cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2295-305
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17664529-1-Acylglycerol-3-Phosphate O-Acyltransferase, pubmed-meshheading:17664529-Animals, pubmed-meshheading:17664529-CHO Cells, pubmed-meshheading:17664529-Carcinoma, Hepatocellular, pubmed-meshheading:17664529-Cell Line, pubmed-meshheading:17664529-Cholesterol, pubmed-meshheading:17664529-Cricetinae, pubmed-meshheading:17664529-Cricetulus, pubmed-meshheading:17664529-Cytoplasm, pubmed-meshheading:17664529-Enzyme Inhibitors, pubmed-meshheading:17664529-Esterases, pubmed-meshheading:17664529-Humans, pubmed-meshheading:17664529-Hydrolysis, pubmed-meshheading:17664529-Lipase, pubmed-meshheading:17664529-Lipoproteins, pubmed-meshheading:17664529-Liver Neoplasms, pubmed-meshheading:17664529-Nucleic Acid Hybridization, pubmed-meshheading:17664529-Phospholipids, pubmed-meshheading:17664529-Triglycerides
pubmed:year
2007
pubmed:articleTitle
CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells.
pubmed:affiliation
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural