Modulating mitochondrial dynamics ameliorates left ventricular dysfunction by suppressing diverse cell death pathways after diabetic cardiomyopathy

Figure 1. Mitochondrial fission is activated whereas mitochondrial fusion is inhibited during DCM. A-C. RNA was isolated from heart tissues after DCM. Then, the transcription of Fis1, Mff and Drp1 was determined by qPCR. D-F. RNA was isolated from heart tissues after DCM. Then, the transcription of Mfn1, Mfn2 and Opa1 was determined by qPCR. *p<0.05.

Figure 2. Inhibition of Mitochondrial Fission Attenuates Cardiac Injury and Cardiomyocyte Apoptosis. To investigate the effects of mitochondrial fission, the mice were administered low dose of Mdivi-1 (0.1 mg/kg) or high dose of Mdivi-1 (1 mg/kg) 12 hours prior to DCMinduction. A-C. Heart function was measured by echocardiography. D-F. ELISA kits were used to evaluate the levels of TnT, CK-MB and LDH in the serum of mice. G. The activity of caspase-3 was determined by an ELISA kit. H. HE staining of myocardium. *p<0.05.

Figure 3. Activation of Mitochondrial Fusion is Linked to Cardiomyocyte Protection. To investigate the effects of mitochondrial fusion, the mice were administered low dose of Ginsenoside Rg1 (Grg1, 1mg/Kg) or high dose of Ginsenoside Rg1 (Grg1, 10 mg/kg) 12 hours prior to DCM induction. A-C. Heart function was measured by echocardiography. D-F. ELISA kits were used to evaluate the levels of TnT, CK-MB and LDH in the serum of mice. G. The activity of caspase-3 was determined by an ELISA kit. H. HE staining of myocardium. *p<0.05.

Figure 4. Inhibition of Mitochondrial Fission Enhances Mitochondrial Function. HL-1 cells were treated with hypoxia for 6 hrs. To inhibit the activity of mitochondrial fission, cells were treated with low dose of Mdivi-1 (0.5 nM) or high dose of Mdivi-1 (5 nM) 6 hours prior to high-glucose (25 mM D-glucose) treatment. A. Mitochondrial membrane potential was determined by immunofluorescence. B. ROS production was determined by DHE staining. C. The concentration of glucose in the medium was measured by ELISA. D. ATP production was determined by ELISA. *p<0.05.

Figure 5. Activation of Mitochondrial Fusion Maintains Mitochondrial Integrity. To activate the activity of mitochondrial fusion, cells were treated with low dose of Ginsenoside Rg1 (GRg1, 1 mM) or high dose of Ginsenoside Rg1 (GRg, 10 mM) 6 hours prior to high-glucose (25 mM D-glucose) treatment. A. Mitochondrial membrane potential was determined by immunofluorescence. B. ROS production was determined by DHE staining. C. The concentration of glucose in the medium was measured by ELISA. D. ATP production was determined by ELISA. *p<0.05.