Increased Diabetes Complications in a Mouse Model of Oxidative Stress Due to ‘Mismatched’ Mitochondrial DNA

Figures

• 

  Figure 1. Animal characteristics. Measurements of glycemia. (A). Blood glucose levels of the four mouse groups on the day of sacrifice. The bars represent the concentrations of glucose expressed as mean values ± standard error of the mean of the group of 10 animals. (B). Levels of HbA1c of the four mouse groups on the day of sacrifice. The bars represent the percentage of glycated HbA1c as mean values ± standard error of the mean of the group of 10 animals. (C). Measurements of body weights. Body mass of the four mouse groups on the day of sacrifice. The bars represent the weights of the mice expressed as mean values ± standard error of the mean of the group of 10 animals. (D). Measurements of heart weight, and (E). kidney weight of the four mouse groups expressed as percentage of the body weight. The bars represent the weights as mean values ± standard error of the mean of the group of 10 animals.

• 

  Figure 2. Measurements of renal and cardiac oxidative stress and fibrosis. (A). The levels of 3-nitrotyrosine in renal tissues obtained by quantification of the positive immunostaining. The bars represent the proportional areas stained positive for 3-nitrotyrosine expressed as mean values ± standard error of the mean of 10 animals. Representative images for the localization of 3-nitrotyrosine in renal tissues, as assessed by the proportional area of positive immunostaining in the 4 groups of mice are shown in the top image panel. (B). Measurements of renal interstitial fibrosis. The levels of intertubular interstitial collagen in renal tissues obtained by quantification of the positive pircrosirus red staining. The bars represent the proportional area stained positive for intertubular interstitial collagen expressed as mean values ± standard error of the mean of 10 animals. Representative images for the localization of intertubular interstitial collagen fibers in renal tissues, are shown in the second from top image panel. (C). Measurements of renal glomerular sclerosis, as assessed by the grading of periodic acid-Schiff (PAS) staining of the glomeruli in the 4 groups of mice. The bars…

• 

  Figure 3. Measurements of cardiac systolic functions. (A). Maximal ADP-stimulated respiration rate in heart mitochondria from non-diabetic WT and XM. (B). Preload recruitable stroke work (PRSW) of the four mouse groups on the day of sacrifice. The bars represent the levels of PRSW in milliwalts (mW) expressed as mean values ± standard error of the mean of the group of 10 animals. (C). Left ventricular fractional area change (FAC) of the four mouse groups on the day of sacrifice. The bars represent the percentage of FAC as mean values ± standard error of the mean of the group of 10 animals. (D). The percentage of ejection fraction of the four mouse groups on the day of sacrifice. The bars represent the percentage of ejection fraction as mean values ± standard error of the mean of the group of 10 animals. (E). Left ventricular end-systolic volume (LVESV) of the four mouse groups on the day of sacrifice. The bars represent the levels of LVESV in microliter (μL) expressed as mean values ± standard error of the mean of the group of 10 animals. (F). Left ventricular activation time (LVA) of the four mouse groups on the day of sacrifice. The bars represent the LVA in seconds (s) as mean values ±…

• 

  Figure 4. Measurements of renal function. Measurements of renal function. (A). Albumin to creatinine ratio (UACR) in mouse urine samples. The bars represent the UACR levels expressed as mean values ± standard error of the mean of 10 animals. (B). The concentrations of creatinine in mouse plasma samples. The bars represent the levels of plasma creatinine expressed as mean values ± standard error of the mean of 10 animals.

• 

  Figure 5. Measurements of skin AGEs and correlations of fibrosis, nitrotyrosine and AGEs. The level of CML (A) and Pentosidine (B) in the animal skin extracted from the 4 mouse groups upon sacrifice. CML level is expressed as mmol per mole of Lysine and Pentosidine level is expressed as ± mol per mole of Lysine. The bars represent the AGE levels as mean values ± standard error of the mean of the group of 10 animals (ANOVA - Bonferroni). (C). Correlation of heart fibrosis and renal nitrotyrosine. (D). Correlation of renal fibrosis and skin CML. (E). Corelation of skin CML and renal nitrotyrosine. (F). Correlation of renal fibrosis and skin pentosidine.

• 

  Figure 6. Evidence of Oxidative Stress in kidney of xenomitochondrial mice at baseline. DCFDA fluorescence detection of H2O2/RNS production (A). Isolated kidney mitochondria were incubated alone (mito only); with pyruvate + malate for complex I-linked oxidation (P + M), with pyruvate + malate + rotenone (P + M + R); with succinate for complex II-linked oxidation; and with succinate + rotenone (Succi + R). Kidney MDA levels (B).