BACKGROUND: To investigate whether the effect of hyperglycemia on mitochondrial DNA (mtDNA) content is tissue-specific. METHOD: We compared the mtDNA contents in leg muscle, blood vessel, and peripheral leucocytes in seventeen patients with type 2 diabetes (T2DM) with those of seven controls. We measured 8-hydroxydeoxyguanosine (8-OHdG) expression in the muscles and thiobarbituric acid reactive substance (TBARS) in sera to evaluate oxidative stress. Immunohistochemical detection of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-α), mitochondrial transcription factor A (Tfam), and apoptosis were performed in the muscle tissue. RESULTS: The mtDNA copy number was highest in muscle tissue, followed by blood vessel tissue, and lowest in leucocytes in both the diabetic and control subjects. The diabetic patients had less mtDNA content in the muscle than the controls (2.86±0.33 vs. 3.20±0.14, P=0.025), but more mtDNA content in the leucocytes (2.25±0.26 vs. 1.98±0.06, P=0.04). In both groups, there was a positive correlation between muscle tissue mtDNA content and the expression of 8-OHdG. Patients with T2DM had significantly increased 8-OHdG and TUNEL labeling index and non-significant increases in the expression of PGC1-α and Tfam. CONCLUSION: Oxidative stress stimulates mitochondrial biogenesis but induces a greater degree of apoptosis in diabetic patients, resulting in a decrease in muscle tissue mtDNA content.
BACKGROUND: To investigate whether the effect of hyperglycemia on mitochondrial DNA (mtDNA) content is tissue-specific. METHOD: We compared the mtDNA contents in leg muscle, blood vessel, and peripheral leucocytes in seventeen patients with type 2 diabetes (T2DM) with those of seven controls. We measured 8-hydroxydeoxyguanosine (8-OHdG) expression in the muscles and thiobarbituric acid reactive substance (TBARS) in sera to evaluate oxidative stress. Immunohistochemical detection of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-α), mitochondrial transcription factor A (Tfam), and apoptosis were performed in the muscle tissue. RESULTS: The mtDNA copy number was highest in muscle tissue, followed by blood vessel tissue, and lowest in leucocytes in both the diabetic and control subjects. The diabeticpatients had less mtDNA content in the muscle than the controls (2.86±0.33 vs. 3.20±0.14, P=0.025), but more mtDNA content in the leucocytes (2.25±0.26 vs. 1.98±0.06, P=0.04). In both groups, there was a positive correlation between muscle tissue mtDNA content and the expression of 8-OHdG. Patients with T2DM had significantly increased 8-OHdG and TUNEL labeling index and non-significant increases in the expression of PGC1-α and Tfam. CONCLUSION: Oxidative stress stimulates mitochondrial biogenesis but induces a greater degree of apoptosis in diabeticpatients, resulting in a decrease in muscle tissue mtDNA content.
Authors: Sadhana A Samant; Hannah J Zhang; Zhigang Hong; Vinodkumar B Pillai; Nagalingam R Sundaresan; Donald Wolfgeher; Stephen L Archer; David C Chan; Mahesh P Gupta Journal: Mol Cell Biol Date: 2013-12-16 Impact factor: 4.272
Authors: María Gómez-Serrano; Emilio Camafeita; Juan A López; Miguel A Rubio; Irene Bretón; Inés García-Consuegra; Eva García-Santos; Jesús Lago; Andrés Sánchez-Pernaute; Antonio Torres; Jesús Vázquez; Belén Peral Journal: Redox Biol Date: 2016-12-18 Impact factor: 11.799
Authors: Lucia Martinez de la Escalera; Ioannis Kyrou; Jana Vrbikova; Voitech Hainer; Petra Sramkova; Martin Fried; Milan K Piya; Sudhesh Kumar; Gyanendra Tripathi; Philip G McTernan Journal: BMC Med Date: 2017-02-16 Impact factor: 8.775