Linked Life Data

21321187

Source:http://linkedlifedata.com/resource/pubmed/id/21321187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-2
pubmed:abstractText
Methylglyoxal (MG), a reactive dicarbonyl molecule, can modify protein to form advanced glycation endproducts. Increased MG level has been implicated in proliferative vascular diseases, but the underlying mechanisms are not clear yet. The serine/threonine kinase, Akt, regulates multiple signaling pathways that control cell proliferation. Using mass spectrometric analysis, we have detected the modification of Akt1 by MG at Cys(77). This structural modification increased Akt1 phosphorylation at Ser(473) and Thr(308). Akt1 phosphorylation and activity were also increased by MG treatment (<50 ?M) in cultured vascular smooth muscle cells (VSMCs). MG treatment of VSMCs led to increased DNA synthesis (EC(50)=5.8 ?M), cell proliferation, phosphorylation of p21 and glycogen synthase kinase-3?/? (GSK-3?/?), and increased cyclin-dependent kinase 2 (CDK2) activity. These effects of MG were significantly inhibited by silencing Akt1 or by an Akt inhibitor. Overexpression of Akt1 Cys(77)Ser mutant in HEK-293 cells increased cell proliferation and DNA synthesis, concurrent with an increase in Akt1 activity, which could not be further augmented by MG treatment. It is concluded that MG-induced VSMC proliferation is mediated by the activation of Akt1 via the modification of Akt1 at Cys(77).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1746-57
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Modification of Akt1 by methylglyoxal promotes the proliferation of vascular smooth muscle cells.
pubmed:affiliation
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't