Objectives Cardiovascular disease is the main cause of death in patients with diabetes. It is reported that Protein kinase C signalling pathway plays a key role in diabetic myocardial and microvascular injury. A-Kinase Anchoring Protein150 (AKAP150) is one of the kinase-binding proteins that strongly increase the activity of kinase. Moreover, AKAP150 is strongly and specifically expressed in cardiac tissue. However, the pathological role of AKAP150 in diabetic cardiomyocyte is unknown. The present study attempts to investigate a role of AKAP150 in diabetic cardiomyocyte and verify that in diabetes, the high expression of p-PKC is not only key to induced cardiomyocyte damage, but abnormal expression of AKAP150 further activates the PKC pathway activity to aggravate cardiomyocyte damage.
Methods Western bolt method was used to observe the level of AKAP150, p-PKC and p-P47phox in diabetic cardiomyocyte of rats. Suppressing AKAP150 by RNAi in cardiomyocyte, we detected the level of p-PKC, p-P47phox and the NADPH oxdiase activity. The ROS and apoptosis levels of cardiomyocyte were assessed. In vitro, the interaction of AKAP150 with PKC was tested by confocal microscope and co-immunoprecipitation analysis.
Results The level of AKAP150 was increased in diabetic cardiomyocyte of rats and relative to PKC’s level. After AKAP150 expression was suppressed, the level of p-PKC and p-P47phox expression and the NADPH oxdiase activity which increased by high glucose stimuli were remarkable decreased, compared with high glucose group (P < 0.05). Moreover, the ROS and apoptosis levels of cardiomyocyte in diabetes were also reduced after AKAP150 expression suppressed, compared with high glucose group (P < 0.05). In vitro, AKAP150 could bind and regulate the activity p-PKC in cardiomyocyte.
Conclusions These data demonstrate, for the first time, we show that AKAP150 is up-regulated in response to high blood glucose stimuli and affects diabetes-induced myocardial damage, and further clarify the mechanism of AKAP150/PKC/P47phox/NADPH/ROS pathway that enhance cardiomyocyte damage.
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