- Email: [email protected]
Circulating mtDNA levels as an early marker for metabolic syndrome
S74 3
D. Rossin et al. / Free Radical Biology and Medicine 108 (2017) S18–S107
Servicio de Laboratorio, Hospital de los Valles. Quito, Ecuador
Keywords: mtDNA; metabolic syndrome; glucose; BMI; ccf-mtDNA
Chronic diseases, infection and physical activity are conditions related with metabolic or oxidative stress and the releasing of mitochondria to circulation by cells. This might be due to apoptosis or transference of mitochondria from one cell to another, either as survival or as tissue repair process. Circulating levels of cell-free mitochondrial DNA (ccf-mtDNA), although controversial, have been used for cancer and sepsis diagnose. The objective of this study was to investigate the relationship between ccf-mtDNA and metabolic syndrome. In this sense, after IRB approval, healthy subjects (n¼ 32) and adults with diabetes (n ¼6) were invited to participate. Body mass index (BMI) was calculated and fasting glucose measured as biomarker of metabolic syndrome. In addition, DNA was extracted from serum and real time PCR used to detect ccf-mtDNA and both parameters were compared. Our data showed that ccf-mtDNA values ranged from 10 to 100 ng/ml in subjects with normal BMI while there were no detectable levels of ccf-mtDNA in samples from overweight subjects and diabetic patients. Glucose levels did not show differences independently of their BMI, but there was an inverse relationship between ccfmtDNA and BMI. In conclusion, our results suggest that ccf-mtDNA might represent an early biomarker to identify people with metabolic syndrome or at risk for future develpment of diabetes.
hypoxia-induced proliferation of PASMC or the development of chronic hypoxia-induced PH. In contrast, MitoQ application attenuated right ventricular remodeling after chronic hypoxic exposure as well as after PAB with regard to development of right heart hypertrophy and dilatation. Accordingly, superoxide levels were increased in the RV after PAB. Conclusion: Increased superoxide concentration mediates acute HPV, while decreased superoxide levels were detected in chronic hypoxia-induced PH. MitoQ may be beneficial under conditions of exaggerated acute HPV and to prevent the development of right heart remodeling. E-mail address: [email protected] (S. Scheibe) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.250
P-166
Ultrastructural Assessment of Mitochondrial Network in the Cultured Skin Fibroblasts from Patients Harboring tRNA Mutations Yen-Chi Chiu 1, Kuang-Jing Huang 1, Shang-Rung Wu 1,2 1
Acknowledgements
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 70101, Taiwan 2 Institute of Oral Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
Financial support provided by USFQ though a Chancello Grant 2015 to AC.
Keywords: Mitochondria; MERRF; MELAS; TEM
E-mail address: [email protected] (E. Teran)
http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.249
P-165
The role of mitochondrial reactive oxygen species in the response of the pulmonary vasculature to hypoxia and right heart remodeling Susan Scheibe 1, Oleg Pak 1, Azadeh Esfandiary 1, Akylbek Sydykov 1, Michael Murphy 2, Norbert Weissmann 1, Natascha Sommer 1 1 2
University of Giessen, Germany MRC Mitochondrial Biology Unit, CB2 0XY Cambridge, UK
Keywords: MitoQ; mitochondrial ROS; pulmonary hypertension; hypoxic pulmonary vasoconstriction
Introduction: Increased release of mitochondrial superoxide has been suggested to mediate acute hypoxic pulmonary vasoconstriction (HPV) as well as chronic hypoxia-induced pulmonary hypertension (PH) and right heart remodeling. Thus, we investigated the superoxide release during HPV, chronic hypoxiainduced PH and after pulmonary arterial banding (PAB), as well as the effect of the mitochondria-targeted antioxidant MitoQ on these processes. Results: Superoxide levels were increased in PASMC during acute hypoxia, and decreased after 5 days of hypoxia. In parallel MitoQ, but not its inactive carrier substance, TPP+, significantly inhibited acute HPV and the rise in superoxide concentration induced by acute hypoxia. However, MitoQ application did not affect the
Single-point mutation of mitochondrial DNA (mtDNA) has been confirmed to be involved in some inheritance of mitochondrial myopathy such as Mitochondrial Encephalopathy, Lactic acidosis, And Stroke-like syndrome (MELAS) and Myoclonic Epilepsy and Ragged-Red Fibers (MERRF). The A-to-G mutation at nucleotide 8344 accounts for 80 to 90% of MERRF syndrome. More than 80% of MELAS patients carry the A3243G mutation. The location of these two point mutations were identified in the transfer RNA (tRNA). It remains unknown why these particular tRNA point mutations caused the abnormal phenotypes. Some studies have demonstrated that Reactive Oxygen Species (ROS) production, alteration in antioxidant defenses and detoxification enzymes is involved in the pathogenesis of MERRF and MELAS syndrome. More and more reports revealed a potential role of oxidative stress within dysregulated mitochondrial network in lesion tissue. However, structural integrity and appropriate distribution and dynamics of mitochondria have to be maintained to execute normal physiological functions. Therefore, we integrated light and electron microscopy to illuminate mosaic mechanisms of the altered mitochondrial distribution and dynamics in cultured skin fibroblasts from patients with mitochondrial tRNA mutations. E-mail address: [email protected] (Y.-C. Chiu) Acknowledgements
This work was supported by the grant MOST 104–2627-M-006002 and MOST 105–2627-M-006-002 from the Ministry of Science and Technology of Taiwan. http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.251
D. Rossin et al. / Free Radical Biology and Medicine 108 (2017) S18–S107
Servicio de Laboratorio, Hospital de los Valles. Quito, Ecuador
Keywords: mtDNA; metabolic syndrome; glucose; BMI; ccf-mtDNA
Chronic diseases, infection and physical activity are conditions related with metabolic or oxidative stress and the releasing of mitochondria to circulation by cells. This might be due to apoptosis or transference of mitochondria from one cell to another, either as survival or as tissue repair process. Circulating levels of cell-free mitochondrial DNA (ccf-mtDNA), although controversial, have been used for cancer and sepsis diagnose. The objective of this study was to investigate the relationship between ccf-mtDNA and metabolic syndrome. In this sense, after IRB approval, healthy subjects (n¼ 32) and adults with diabetes (n ¼6) were invited to participate. Body mass index (BMI) was calculated and fasting glucose measured as biomarker of metabolic syndrome. In addition, DNA was extracted from serum and real time PCR used to detect ccf-mtDNA and both parameters were compared. Our data showed that ccf-mtDNA values ranged from 10 to 100 ng/ml in subjects with normal BMI while there were no detectable levels of ccf-mtDNA in samples from overweight subjects and diabetic patients. Glucose levels did not show differences independently of their BMI, but there was an inverse relationship between ccfmtDNA and BMI. In conclusion, our results suggest that ccf-mtDNA might represent an early biomarker to identify people with metabolic syndrome or at risk for future develpment of diabetes.
hypoxia-induced proliferation of PASMC or the development of chronic hypoxia-induced PH. In contrast, MitoQ application attenuated right ventricular remodeling after chronic hypoxic exposure as well as after PAB with regard to development of right heart hypertrophy and dilatation. Accordingly, superoxide levels were increased in the RV after PAB. Conclusion: Increased superoxide concentration mediates acute HPV, while decreased superoxide levels were detected in chronic hypoxia-induced PH. MitoQ may be beneficial under conditions of exaggerated acute HPV and to prevent the development of right heart remodeling. E-mail address: [email protected] (S. Scheibe) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.250
P-166
Ultrastructural Assessment of Mitochondrial Network in the Cultured Skin Fibroblasts from Patients Harboring tRNA Mutations Yen-Chi Chiu 1, Kuang-Jing Huang 1, Shang-Rung Wu 1,2 1
Acknowledgements
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 70101, Taiwan 2 Institute of Oral Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
Financial support provided by USFQ though a Chancello Grant 2015 to AC.
Keywords: Mitochondria; MERRF; MELAS; TEM
E-mail address: [email protected] (E. Teran)
http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.249
P-165
The role of mitochondrial reactive oxygen species in the response of the pulmonary vasculature to hypoxia and right heart remodeling Susan Scheibe 1, Oleg Pak 1, Azadeh Esfandiary 1, Akylbek Sydykov 1, Michael Murphy 2, Norbert Weissmann 1, Natascha Sommer 1 1 2
University of Giessen, Germany MRC Mitochondrial Biology Unit, CB2 0XY Cambridge, UK
Keywords: MitoQ; mitochondrial ROS; pulmonary hypertension; hypoxic pulmonary vasoconstriction
Introduction: Increased release of mitochondrial superoxide has been suggested to mediate acute hypoxic pulmonary vasoconstriction (HPV) as well as chronic hypoxia-induced pulmonary hypertension (PH) and right heart remodeling. Thus, we investigated the superoxide release during HPV, chronic hypoxiainduced PH and after pulmonary arterial banding (PAB), as well as the effect of the mitochondria-targeted antioxidant MitoQ on these processes. Results: Superoxide levels were increased in PASMC during acute hypoxia, and decreased after 5 days of hypoxia. In parallel MitoQ, but not its inactive carrier substance, TPP+, significantly inhibited acute HPV and the rise in superoxide concentration induced by acute hypoxia. However, MitoQ application did not affect the
Single-point mutation of mitochondrial DNA (mtDNA) has been confirmed to be involved in some inheritance of mitochondrial myopathy such as Mitochondrial Encephalopathy, Lactic acidosis, And Stroke-like syndrome (MELAS) and Myoclonic Epilepsy and Ragged-Red Fibers (MERRF). The A-to-G mutation at nucleotide 8344 accounts for 80 to 90% of MERRF syndrome. More than 80% of MELAS patients carry the A3243G mutation. The location of these two point mutations were identified in the transfer RNA (tRNA). It remains unknown why these particular tRNA point mutations caused the abnormal phenotypes. Some studies have demonstrated that Reactive Oxygen Species (ROS) production, alteration in antioxidant defenses and detoxification enzymes is involved in the pathogenesis of MERRF and MELAS syndrome. More and more reports revealed a potential role of oxidative stress within dysregulated mitochondrial network in lesion tissue. However, structural integrity and appropriate distribution and dynamics of mitochondria have to be maintained to execute normal physiological functions. Therefore, we integrated light and electron microscopy to illuminate mosaic mechanisms of the altered mitochondrial distribution and dynamics in cultured skin fibroblasts from patients with mitochondrial tRNA mutations. E-mail address: [email protected] (Y.-C. Chiu) Acknowledgements
This work was supported by the grant MOST 104–2627-M-006002 and MOST 105–2627-M-006-002 from the Ministry of Science and Technology of Taiwan. http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.251