Linked Life Data

14966364

Source:http://linkedlifedata.com/resource/pubmed/id/14966364

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-17
pubmed:abstractText
Hyperglycemia and mannitol activate protein kinase C (PKC) and induce mesangial cell hypocontractility that subsequently may modulate renal function. Since focal adhesion kinase (FAK) activation is known to be linked with PKC activity, FAK may also be involved in mesangial cell contraction. To facilitate our understanding of the PKC- and FAK-modulating mechanism, we developed an in vitro model of mouse mesangial cell hypocontractility induced by hyperglycemia or mannitol. Mouse mesangial cells (CRL-1927) were exposed to: normal D-glucose (group N), high D-glucose (group H), and control groups at the same osmolality as H plus L-glucose (group L) and mannitol (group M). Changes in the planar surface area of cells in response to 1 microM phorbol 12-myristate 13-acetate (PMA) were determined. Western blot analyses for PKC, phosphorylated (p)-PKC, tyrosine phosphorylation, FAK, and p-FAK were done on each of these four groups. The effects of mannitol in various doses on cell contraction and activation of PKC and FAK were also assayed. The planar surface areas of groups H and M both showed an attenuated change in response to PMA stimulation. Before PMA stimulation, the baseline PKC expression of groups H and M showed a higher expression of p-PKC alpha and delta than that seen in group N (p < 0.05). Results of tyrosine phosphorylation and immunoprecipitation showed that FAK may be involved in this contraction process. The total amount of FAK showed no significant difference among the four experimental groups; however, p-FAK was found to have significantly increased in group M (p < 0.05). The use of PKC and tyrosine kinase inhibitors reduced PMA-induced mesangial cell contraction in all four groups. Activation of PKC alpha, delta, and FAK with the resultant inhibition of mesangial cell contraction by mannitol was found to be dose-dependent. These results may provide a correlation between increased expression of several PKC isoforms and, in particular, increased phosphorylation levels of PKC alpha and delta and hypocontractility induced by high glucose and mannitol treatment. Furthermore, the mannitol-induced hypocontractility involving PKC and FAK occurred in a dose-dependent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine..., http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Mannitol, http://linkedlifedata.com/resource/pubmed/chemical/Prkca protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Prkcd protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-delta, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
pubmed:status
MEDLINE
pubmed:issn
1021-7770
pubmed:author
pubmed:copyrightInfo
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
142-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:articleTitle
Attenuation of mouse mesangial cell contractility by high glucose and mannitol: involvement of protein kinase C and focal adhesion kinase.
pubmed:affiliation
Graduate Institute of Medical Sciences, National Defense Medical Center, and Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't