Source:http://linkedlifedata.com/resource/pubmed/id/20044781
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2010-3-26
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pubmed:abstractText |
PKC-beta inhibitor Ruboxistaurin (RBX or LY333531) can be used to reverse diabetic microvascular complication. However, it has not been previously established whether RBX can protect against ischemia/reperfusion (I/R) injury of cardiac microvessels in diabetic rats. STZ-induced diabetic rats were randomized into four groups and underwent I/R procedures. Cardiac barrier function and the region of cardiac microvascular lesion were examined. Cell monolayer barrier function was detected in cultured cardiac microvascular endothelial cells (CMECs) subjected to simulated I/R (SI/R). PKC-beta siRNA was transfected into CMECs to silence PKC-beta. Apoptosis Index of CMECs was detected by TUNEL assay and phosphor-LIMK2 protein expression was examined by Western blot analysis. RBX and insulin administration significantly reduced the cardiac microvascular lesion region and Apoptosis Index of endothelial cells (all P < 0.05 vs. no-treatment group). RBX decreased phosphor-LIMK2 expression (P < 0.05 vs. no-treatment group). RBX pretreatment and transfection with PKC-beta siRNA induced a rapid barrier enhancement in CMECs monolayer as detected by increased transendothelial electrical resistance (TER) and decreased FITC-dextran clearance (all P < 0.05 vs. no-treatment group). Meanwhile, RBX pretreatment and transfection with PKC-beta siRNA significantly decreased TUNEL positive CMECs and phosphor-LIMK2 expression in cultured CMECs (all P < 0.05 vs. no-treatment group). RBX pretreatment reduced F-actin/G-actin in cultured CMECs, reproducing the same effect as PKC-beta siRNA. These data indicate that PKC-beta inhibitor (RBX) may be helpful in attenuating the risk of severe cardiac microvascular I/R injury in diabetic rats partly due to its maintenance of endothelial barrier function and anti-apoptotic effect.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Lim Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Limk2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta,
http://linkedlifedata.com/resource/pubmed/chemical/ruboxistaurin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1573-675X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
488-98
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pubmed:meshHeading |
pubmed-meshheading:20044781-Actins,
pubmed-meshheading:20044781-Animals,
pubmed-meshheading:20044781-Apoptosis,
pubmed-meshheading:20044781-Diabetes Mellitus, Experimental,
pubmed-meshheading:20044781-Down-Regulation,
pubmed-meshheading:20044781-Electric Impedance,
pubmed-meshheading:20044781-Endothelial Cells,
pubmed-meshheading:20044781-Glucose,
pubmed-meshheading:20044781-Indoles,
pubmed-meshheading:20044781-Lim Kinases,
pubmed-meshheading:20044781-Male,
pubmed-meshheading:20044781-Maleimides,
pubmed-meshheading:20044781-Microvessels,
pubmed-meshheading:20044781-Myocardium,
pubmed-meshheading:20044781-Protective Agents,
pubmed-meshheading:20044781-Protein Kinase C,
pubmed-meshheading:20044781-Protein Kinase Inhibitors,
pubmed-meshheading:20044781-Rats,
pubmed-meshheading:20044781-Rats, Sprague-Dawley,
pubmed-meshheading:20044781-Reperfusion Injury
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pubmed:year |
2010
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pubmed:articleTitle |
A PKC-beta inhibitor protects against cardiac microvascular ischemia reperfusion injury in diabetic rats.
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pubmed:affiliation |
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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