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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
- Source :
- Cardiovascular Diabetology, Cardiovascular Diabetology, Vol 8, Iss 1, p 8 (2009)
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Background High 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. Objectives To study the influence of high glucose on the structure, function and signal transduction pathway of PKC (Protein Kinase C)/NF-κB(Nuclear factor-κB)/c-fos in cultured cardiomyocytes. Methods Using 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 glucose(25.5 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. Results Cardiomyocytes 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. Conclusion High 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.
- Subjects :
- lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
c-Fos
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
chemistry.chemical_compound
Western blot
Internal medicine
Diabetic cardiomyopathy
medicine
Animals
Myocyte
Myocytes, Cardiac
Cells, Cultured
Protein Kinase C
Protein kinase C
Original Investigation
biology
medicine.diagnostic_test
business.industry
NF-kappa B
NF-κB
medicine.disease
Rats
Glucose
Endocrinology
Animals, Newborn
L-Glucose
chemistry
lcsh:RC666-701
biology.protein
Signal transduction
Cardiology and Cardiovascular Medicine
business
Proto-Oncogene Proteins c-fos
Signal Transduction
Subjects
Details
- ISSN :
- 14752840
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Diabetology
- Accession number :
- edsair.doi.dedup.....b83daaee5a33ee75e931ced6eb9a3c43