Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-9-15
pubmed:abstractText
Glucocorticoids are widely used as anti-inflammatory and chemotherapeutic agents. However, prolonged use of glucocorticoids leads to osteoporosis. This study was designed to examine the mechanism of dexamethasone (DEX)-induced apoptosis in murine osteoblastic MC3T3-E1 cells. Total RNA was extracted from MC3T3-E1 cells treated with 10(-7) M DEX for 6 h. DEX exerted a variety of effects on apoptotic gene expression in osteoblasts. Ribonuclease protection assays (RPA) revealed that DEX upregulated mRNA levels of caspases-1, -3, -6, -8, -11, -12, and bcl-XL. Western blot analysis showed enhanced processing of these caspases, with the appearance of their activated enzymes 8 h after DEX treatment. In addition, DEX also induced the activation of caspase-9. DEX elevated the levels of cleaved poly(ADP-ribose) polymerase and lamin A, a caspase-3 and a caspase-6 substrate, respectively. Expression of bcl-XL protein level was upregulated by DEX. Cytochrome c release was detected in the cytosol of DEX-treated cells. Furthermore, caspase-3 enzyme activity was elevated by 2-fold after DEX treatment for 7 h. Finally, early apoptotic cells were detected in cells treated with DEX for 3 h. Our results demonstrate that DEX-induced apoptosis involves gene activation of a number of caspases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
1642
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-85
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12972296-Animals, pubmed-meshheading:12972296-Apoptosis, pubmed-meshheading:12972296-Caspases, pubmed-meshheading:12972296-Cytochrome c Group, pubmed-meshheading:12972296-Dexamethasone, pubmed-meshheading:12972296-Enzyme Induction, pubmed-meshheading:12972296-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12972296-Lamin Type A, pubmed-meshheading:12972296-Mice, pubmed-meshheading:12972296-Osteoblasts, pubmed-meshheading:12972296-Osteoporosis, pubmed-meshheading:12972296-Poly(ADP-ribose) Polymerases, pubmed-meshheading:12972296-Proteins, pubmed-meshheading:12972296-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12972296-RNA, Messenger, pubmed-meshheading:12972296-Reaction Time, pubmed-meshheading:12972296-Transcriptional Activation, pubmed-meshheading:12972296-Up-Regulation, pubmed-meshheading:12972296-bcl-X Protein
pubmed:year
2003
pubmed:articleTitle
Dexamethasone induces caspase activation in murine osteoblastic MC3T3-E1 cells.
pubmed:affiliation
Osteoporosis Center, James H. Quillen College of Medicine, East Tennessee State University, and Veterans Affairs Medical Center, Box 70432, Johnson City, TN 37614, USA. chua.chu@med.va.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't