Diabetogia: Akap1 defects mediated by NDUFS1 caused by mitochondrial dysfunction and apoptosis in mice exacerbated diabetic cardiomyopathy.

The !-----diabetic cardiomyopathy is characterized by increased oxidative damage and mitochondrial dysfunction, which in turn leads to an increased risk of heart failure in diabetic patientsthe study aims to explore the role and mechanism of AKAP1 in diabetic cardiomyopathy because a-kinase anchor protein 121 (AKAP1) is positioned in the mitochondrial membrane and plays a key role in the regulation of the online granule functionthe role of AKAP1 in diabetic cardiomyopathy is discussed in two methods: loss of function and function acquisitioninjected streptococcus (STZ) into akap1-KO mice and their wild-type (WT) identical mice to induce diabetesin addition, the primary heart muscle cells treated with high sugar were used as a cellular model for diabetesan echocardiogram to check the heart's functionAkap1 is expressed by injecting adenovirus 9 carrying Akap1 (AAV9-Akap1)use LC-MS/MS analysis and functional experiments to explore its potential molecular mechanismsresults showed that the expression of AKAP1 declined in the heart of stz-induced diabetic micecompared to wild diabetic mice, Akap1-KO significantly aggravated heart dysfunction in diabetic mice treated by STZ,KO /STZ, 51.6% and 41.6%, respectively)mechanism, a lack of Akap1 impairs mitochondrial breathing function, which is characterized by a decrease in ATP productionin addition, akap1 deficiency increases the apoptosis of myocardial cells by increasing the production of mitochondrial reactive oxygen (ROS)immunoprecipitation and mass spectrometry analysis showed that AKAP1 interacted with NADH-ubiquinone oxidoreductase 75 kDa subki (NDUFS1)specifically, Akap1 deficiency inhibits the activity of complex I by preventing NDUFS1 from moving from the cytoplasm to the mitochondriaAkap1 deficiency is also associated with a decrease in ATP production and an increase in mitochondrial apoptosis, by contrast, the recovery of AKAP1 expression in the heart of a diabetic mouse treated by STZ promoted the translocation of NDUFS1 to mitochondrial and reduced LVEFour study is the first to show that a lack of Akap1 hinders mitochondrial translocation of NDUFS1, leading to mitochondrial dysfunction and apoptosis of myocardial cells, which can exacerbate diabetic cardiomyopathyour results show that Akap1 is potentially therapeutic for cardiomyopathy in diabetic patients.