Linked Life Data

18270325

Source:http://linkedlifedata.com/resource/pubmed/id/18270325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-4-9
pubmed:abstractText
Ceramide, a tumor-suppressor lipid, is generated by sphingomyelin hydrolysis or by de novo synthesis when cells are activated by various stress stimuli as well as when cancer cells are subjected to genotoxic chemotherapy. Ceramide may modulate apoptotic signaling pathways; however, its transcription-dependent effects remain unclear. Our data showed that actinomycin D partially inhibited ceramide-induced apoptosis. Using microarray analysis, we found that ceramide up-regulated a tumor suppressor gene called thioredoxin-interacting protein (Txnip). Similarly, the chemotherapeutic agent etoposide induced Txnip expression en route to apoptosis, which was blocked by inhibitors of ceramide production. Txnip colocalized with thioredoxin and reduced its activity, which caused dissociation of thioredoxin from apoptosis signal-regulating kinase 1 (ASK1). Cells expressing ASK1 siRNA were more resistant to ceramide-induced apoptosis. Ceramide caused ASK1-regulated p38 mitogen-activated protein kinase (MAPK) and JNK activation, as well as activation of the endoplasmic reticulum (ER) stress cascade, and pharmacologic or siRNA-mediated inhibition of p38 MAPK or JNK partially reduced ceramide-induced mitochondria-mediated apoptosis. Furthermore, ceramide-induced ASK1, p38, and JNK phosphorylation and cell apoptosis were inhibited by Txnip siRNA transfection. Taken together, we show that ceramide exhibits a mechanism of transcriptional regulation involving up-regulation of Txnip expression, also induced by etoposide, which results in ASK1 activation, ER stress, and p38 and JNK phosphorylation, all leading to apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4365-74
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:18270325-Animals, pubmed-meshheading:18270325-Apoptosis, pubmed-meshheading:18270325-Carrier Proteins, pubmed-meshheading:18270325-Ceramides, pubmed-meshheading:18270325-Dactinomycin, pubmed-meshheading:18270325-Down-Regulation, pubmed-meshheading:18270325-Enzyme Activation, pubmed-meshheading:18270325-Etoposide, pubmed-meshheading:18270325-Gene Expression Regulation, Leukemic, pubmed-meshheading:18270325-Humans, pubmed-meshheading:18270325-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:18270325-Jurkat Cells, pubmed-meshheading:18270325-MAP Kinase Kinase Kinase 5, pubmed-meshheading:18270325-Mice, pubmed-meshheading:18270325-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18270325-Phosphorylation, pubmed-meshheading:18270325-Protein Transport, pubmed-meshheading:18270325-RNA, Messenger, pubmed-meshheading:18270325-Thioredoxins, pubmed-meshheading:18270325-Transcription, Genetic, pubmed-meshheading:18270325-Up-Regulation, pubmed-meshheading:18270325-p38 Mitogen-Activated Protein Kinases
pubmed:year
2008
pubmed:articleTitle
Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway.
pubmed:affiliation
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't