Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-12-30
pubmed:abstractText
Double-stranded RNA-dependent protein kinase (PKR) is a participant in the cellular antiviral response and phosphorylates the alpha-subunit of eukaryotic translation initiation factor 2alpha (eIF-2alpha) to block protein synthesis. Treatment of human osteosarcoma cell line MG63 cells with a serine and threonine protein phosphatase inhibitor, okadaic acid, at the concentration of 100 nM, but not at 20 nM, induced apoptosis. To investigate the functional relationship between phosphatases and apoptosis, we examined the phosphorylation levels of PKR and eIF-2alpha by Western blot analysis. During treatment of cells with it at the higher concentration (100 nM), okadaic acid increased the level of phosphorylated PKR in MG63 cells, this kinase phosphorylating eIF-2alpha. However, at the lower concentration (20 nM), okadaic acid did not affect the level of phosphorylated PKR. In the cells treated with 100 nM okadaic acid, activation of NF-kappaB also occurred. Even though inhibition of translation occurred simultaneously in MG63 cells, the expression of pro-apoptotic proteins Fas and Bax was not affected by 100 nM okadaic acid in these cells. We concluded that the inhibition of translation decreased anti-apoptotic protein expression, thus resulting in apoptosis. Our results also suggest that the inhibition of the protein phosphatase activity by okadaic acid induced apoptosis in MG63 cells through PKR and eIF-2alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-924X
pubmed:author
pubmed:issnType
Print
pubmed:volume
136
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
433-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15625311-Apoptosis, pubmed-meshheading:15625311-Blotting, Western, pubmed-meshheading:15625311-Cell Line, Tumor, pubmed-meshheading:15625311-DNA, pubmed-meshheading:15625311-Dose-Response Relationship, Drug, pubmed-meshheading:15625311-Electrophoresis, Agar Gel, pubmed-meshheading:15625311-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:15625311-Eukaryotic Initiation Factor-2, pubmed-meshheading:15625311-Humans, pubmed-meshheading:15625311-Microscopy, Phase-Contrast, pubmed-meshheading:15625311-NF-kappa B, pubmed-meshheading:15625311-Okadaic Acid, pubmed-meshheading:15625311-Osteoblasts, pubmed-meshheading:15625311-Phosphorylation, pubmed-meshheading:15625311-Protein Biosynthesis, pubmed-meshheading:15625311-Pyrazoles, pubmed-meshheading:15625311-Pyrimidines, pubmed-meshheading:15625311-Time Factors, pubmed-meshheading:15625311-eIF-2 Kinase
pubmed:year
2004
pubmed:articleTitle
Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2alpha pathway in human osteoblastic MG63 cells.
pubmed:affiliation
Department of Anatomy, School of Dentistry, The University of Tokushima, Kuramoto, Tokushima 770-8504, Japan. morimoto@dent.tokushima-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't