Linked Life Data

19937732

Source:http://linkedlifedata.com/resource/pubmed/id/19937732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-28
pubmed:abstractText
Phospholipase A(2) (PLA(2)) from Naja naja atra venom induced apoptotic death of human leukemia K562 cells. Degradation of procaspases, production of tBid, loss of mitochondrial membrane potential, Bcl-2 degradation, mitochondrial translocation of Bax, and cytochrome c release were observed in PLA(2)-treated cells. Moreover, PLA(2) treatment increased Fas and FasL protein expression. Upon exposure to PLA(2), activation of p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun NH(2)-terminal kinase) was found in K562 cells. SB202190 (p38 MAPK inhibitor) pretreatment enhanced cytotoxic effect of PLA(2) and led to prolonged JNK activation, but failed to affect PLA(2)-induced upregulation of Fas and FasL protein expression. Sustained JNK activation aggravated caspase8/mitochondria-dependent death pathway, downregulated Bcl-2 expression and increased mitochondrial translocation of Bax. SP600125 (JNK inhibitor) abolished the cytotoxic effect of PLA(2) and PLA(2)-induced autocrine Fas death pathway. Transfection ASK1 siRNA and overexpression of dominant negative p38alpha MAPK proved that ASK1 pathway was responsible for PLA(2)-induced p38 MAPK and JNK activation and p38alpha MAPK activation suppressed dynamically persistent JNK activation. Downregulation of FADD abolished PLA(2)-induced procaspase-8 degradation and rescued viability of PLA(2)-treated cells. Taken together, our results indicate that JNK-mediated autocrine Fas/FasL apoptotic mechanism and modulation of Bcl-2 family proteins are involved in PLA(2)-induced death of K562 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1097-4644
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-54
pubmed:meshHeading
pubmed-meshheading:19937732-Antigens, CD95, pubmed-meshheading:19937732-Apoptosis, pubmed-meshheading:19937732-Blotting, Western, pubmed-meshheading:19937732-Cell Separation, pubmed-meshheading:19937732-Cell Survival, pubmed-meshheading:19937732-Cobra Venoms, pubmed-meshheading:19937732-Enzyme Activation, pubmed-meshheading:19937732-Enzyme Inhibitors, pubmed-meshheading:19937732-Fas Ligand Protein, pubmed-meshheading:19937732-Flow Cytometry, pubmed-meshheading:19937732-Humans, pubmed-meshheading:19937732-K562 Cells, pubmed-meshheading:19937732-Leukemia, pubmed-meshheading:19937732-MAP Kinase Kinase 4, pubmed-meshheading:19937732-Membrane Potential, Mitochondrial, pubmed-meshheading:19937732-Phospholipases A2, pubmed-meshheading:19937732-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19937732-RNA Interference, pubmed-meshheading:19937732-Signal Transduction, pubmed-meshheading:19937732-Transfection, pubmed-meshheading:19937732-bcl-2-Associated X Protein
pubmed:year
2010
pubmed:articleTitle
Taiwan cobra phospholipase A2-elicited JNK activation is responsible for autocrine fas-mediated cell death and modulating Bcl-2 and Bax protein expression in human leukemia K562 cells.
pubmed:affiliation
Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't