The signal transduction pathway of PKC-NF-κB-c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal ratsReportar como inadecuado




The signal transduction pathway of PKC-NF-κB-c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cardiovascular Diabetology

, 8:8

First Online: 11 February 2009Received: 30 November 2008Accepted: 11 February 2009

Abstract

BackgroundHigh glucose could induce structure and function change in cardiomyocytes, PKC plays a core effect in the onset and progression of diabetic cardiomyopathy, but its underlying downstream signal transduction pathway is still not completely understood.

ObjectivesTo study the influence of high glucose on the structure, function and signal transduction pathway of PKC Protein Kinase C-NF-κBNuclear factor-κB-c-fos in cultured cardiomyocytes.

MethodsUsing cultured cardiomyocytes of neonatal Sprague-Dawley rats as a model, groups were divided into: control group glucose: 5 mmol-L; high glucose group glucose: 10 mmol-L, 15 mmol-L, 20 mmol-L, 25.5 mmol-L; equimolar mannital group 5 mmol-L glucose + 20.5 mmol-L maninital; high glucose25.5 mmol-L add PKC inhibitor Ro-31-8220, 50 nmol-L; high glucose 25.5 mmol-L add NF-κB inhibitor BAY11-7082, 5 μmol-L. The cellular contracting frequency and volumes were measured and the expression of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2, NF-κB, p-NF-κB, TNF-α tumor necrosis factor-α and c-fos were measured by western blot or RT-PCR.

ResultsCardiomyocytes cultured in high glucose level, but not iso-osmotic mannital, showed an increased pulsatile frequency and higher cellular volumes consistent with the increased glucose levels, and also higher expression of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2, NF-κB, p-NF-κB, TNF-α and c-fos. The addition of Ro-31-8220 and BAY11-7082 could partly reverse these changes induced by high glucose level.

ConclusionHigh glucose significantly increased the pulsatile frequency and cellular volumes of cultured cardiomyocytes via PKC-NF-κB-c-fos pathway, which might lead to diabetic cardiomyopathy.

AbbreviationsPKCProtein Kinase C

NF-κBNuclear factor-κB

TNF-αtumor necrosis factor-α

DAGdiacylglycerol

PLAphospholipase a

PIphosphatidyl inositol

MAPmitogen-activated protein

TBSTris-buffered solution

TBSTTris-buffered solution containing 0.1%v-v Tween 20

ECLenhanced chemiluminescence

MAPKmitogen-activated protein kinase

AP-1activator protein-1

TGF-βtransforming growth factor-β

IKKI-κB kinase

IêBαinhibitory protein α of NF-κB.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-8-8 contains supplementary material, which is available to authorized users.

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Autor: Wang Min - Zhang Wen Bin - Zhou Bin Quan - Zhu Jun Hui - Fu Guo Sheng

Fuente: https://link.springer.com/article/10.1186/1475-2840-8-8







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