Reverse effect of protein kinase C inhibitor Ro-31-8220 on the hypertrophy of cardiomyocytes of neonatal rats induced by high glucose levels
ZHANG Wen-bin1; CHEN Ju2; WANG Min1; ZHOU Bin-quan1; FU Guo-sheng1
1Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China; 2Department of Cardiology, People’s Hospital of Zhuji, Zhuji 311800, China. E-mail: fugs@medmail.com.cn
Abstract：AIM: To study the effect of protein kinase C (PKC) inhibitor Ro-31-8220 on the hypertrophy of cardiomyocytes of neonatal rats induced by high glucose levels, and to investigate the role of PKC and its downstream signal transduction pathway. METHODS: Using cultured neonatal cardiac myocytes as a model, the cells were divided into: (1) control group (glucose 5.5 mmol/L); (2) different high glucose level (10 mmol/L,15 mmol/L, 20 mmol/L, 25.5 mmol/L); (3) high glucose level (25.5 mmol/L) + PKC inhibitor Ro-31-8220 (50 nmol/L); (4) high glucose level (25.5mmol/L) + NF-κB inhibitor (BAY11-7082, 5 mmol/L). The cellular diameters and protein level were measured and the expression of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2, NF-κB and c-Fos were determined by Western blotting. RESULTS: Neonatal cardiomyocytes cultured in high glucose concentration showed increased cellular diameters, protein level and higher expressions of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2, NF-κB and c-Fos, which was consistent with the increased glucose levels and had statistical significance compared to control group (P<0.01). PKC inhibitor Ro-31-8220 reversed these changes induced by high glucose concentration as showed by decreased cellular diameters, protein level and expression of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2, NF-κB and c-Fos, which had statistical significance compared to high glucose groups (P<0.01). CONCLUSION: High glucose levels induce hypertrophy of cardiomyocytes. PKC inhibitor Ro-31-8220 reverses the effect of high glucose on the cardiac myocytes, which may be via PKC/NF-κB/c-Fos pathway.
张文斌;陈炬;王敏;周斌全;傅国胜. 蛋白激酶C抑制剂Ro-31-8220逆转高糖诱导乳鼠心肌细胞肥大的作用及其相关机制[J]. 中国病理生理杂志, 2009, 25(8): 1481-1485.
ZHANG Wen-bin; CHEN Ju; WANG Min; ZHOU Bin-quan; FU Guo-sheng. Reverse effect of protein kinase C inhibitor Ro-31-8220 on the hypertrophy of cardiomyocytes of neonatal rats induced by high glucose levels. Chin J Pathophysiol, 2009, 25(8): 1481-1485.
