O. Azimzadeh, W. Sievert, J. Merl-Pham, G. Multhoff, M. Atkinson, S. Tapio
{"title":"Perturbation in Cardiac Energy Metabolism is Linked to Radiation-induced Heart Disease","authors":"O. Azimzadeh, W. Sievert, J. Merl-Pham, G. Multhoff, M. Atkinson, S. Tapio","doi":"10.18143/JWMS_V2I2_1893","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1893","url":null,"abstract":"Radiation exposure to the thorax is associated with a markedly increased risk of cardiac morbidity and mortality with a latency period of [1-4]. Although many studies have confirmed the damaging effect of ionizing radiation on the myocardium and cardiac endothelial structure and function, the molecular mechanism behind this damage is not yet elucidated. As cardiac function greatly depends on mitochondrial metabolic activity we investigated radiation-induced cardiac metabolism disordering in general and the role of Peroxisome proliferator-activated receptor alpha (PPAR alpha) in this process in particular. C57BL/6N mice were locally irradiated to the heart at the age of 8 weeks using X-ray doses of 8 and 16 Gy. The mice were sacrificed 16 weeks after irradiation and the changes in the cardiac proteome were quantified using Isotope Coded Protein Label (ICPL). The proteomics data were further analysed using transcriptomics, immunoblotting, bioinformatics, immunohistochemistry, electron microscopy and serum lipid profiling. Significant alterations were observed in proteins involved in cardiac lipid metabolism and mitochondrial oxidative phosphorylation. Ionizing radiation markedly changed the mitochondrial structure and size, characterized by the loss of the mitochondrial matrix. Irradiation increased phosphorylation and ubiquitination status of PPAR alpha resulting in decreased expression of its target proteins involved in energy metabolism and mitochondrial respiratory chain. This study suggests that persistent alteration of cardiac metabolism due to impaired PPAR alpha activity contributes to the heart pathology after radiation activity activity [5].","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117231566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fractions of Khaya grandifoliola C.DC and Entada africana Guill. et Perr. Protect against Acetaminophen (APAP)-induced Liver Damage and Mitochondrial Dysfunction in Rats","authors":"Njayou Frederic Nico, M. F. Paul","doi":"10.18143/JWMS_V2I2_1899","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1899","url":null,"abstract":"Objectives: To investigate the effect of the fractions methylene chloride/methanol 25% (KF25) of K. grandifoliola and 10% (EF10) of E. africana pretreatment against APAP-induced liver damage and mitochondrial dysfunction in rats. Material and Methods: Each plant fraction was orally given to animals for seven days. In dose-response study both fractions were tested at the doses of 25 and 100mg/kg body weight (b.w). In the mitochondria dysfunction study the KF25 and EF10 were administered at 25 and 100 mg/kg b.w, respectively. For both studies, Silymarine was used as reference drug and tested at 100mg/kg b.w. After pretreatment period, animals were intoxicated by oral administration of APAP (1g/kg, b.w) and sacrificed by decapitation. Serum, liver homogenate and mitochondria fraction were prepared for biochemical analyses. Results: Silymarin, KF25 and EF10 exhibited respective percentage of hepatoprotection of 88.65, 86.21 and 86.83% and inhibited liver lipid peroxidation. Levels of liver reduced glutathion, superoxide dismutase, catalase and mitochondrial complexes (II, III and V) enzymes activities decreased upon administration of APAP and mitochondrial swelling were significantly (P<0.05) improved. Conclusions: This study highlights the protective effect of KF25 and EF10 against APAP-induced liver damage. These plant fractions may be good source of compounds for management of drug-induced hepatotoxicity. Key words: Khaya grandifoliola, Entada africana, Inhibition, Mitochondria dysfunction, Acetaminophen.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128918820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of cell protection effects of Twendee X by oxidative stress.","authors":"H. Inufusa","doi":"10.18143/JWMS_V2I2_1900","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1900","url":null,"abstract":"[Purposes] Reactive Oxygen Species (ROS) damages cell and mitochondria (MT) as well. Twendee X (TWX) is a composition consisting of Vitamin C, Glutamine, Cystine or Cysteine, Riboflavin, Succinic acid, Fumaric acid, Coenzyme Q10, and Niacin. TWX strongly reduces ROS (Patent: WIPO WO2013/072441 A1, COMPOSITION FOR PROTECTION AGAINST CELL-DAMAGING EFFECTS). Ant-ROS and cell protection effects of TWX in vivo and vitro were examined. [Experiment] Amount of TWX administrated to mouse was 15-20mg/kg. Mouse: C57BL, male. Parameters of ROS were d-ROMs test (hydrogen peroxide level), BAP test (Biological Antioxidant Potential) and OXY Adsorbent test (Elimination ability of the hypochlorous acid). Cell culture experiments using HepG2 cell line was conducted by ICDD (France). [Data] Administration of TWX to radiation mouse model 3 days and 7days reduced d-ROMs test 65% and 111% respectively. Survival of mouse radiation was significantly prolonged by Twendee X administration. ICDD reported that TWX reduces ROS of cell: 45% and MT: 63%, increase Superoxide Dismutase of cell: 60% and MT: 147%. [Conclusion] ICDD confirmed that TWX is most strong anti-ROS and protection effects from ROS. TWX is a very safe composition for human, and already started human clinical study.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129061353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Delta opioid receptor agonist attenuates Lipopolysaccharide-induced myocardial dysfunction through enhancing mitophagy","authors":"Pin Zhao, Li-nong Yao","doi":"10.18143/JWMS_V2I2_1889","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1889","url":null,"abstract":"Objectives:To explore the molecular mechanisms of the protective effects of δ-opioid receptor agonist DADLE([D-Ala2,D-Leu5]-enkephalin)on myocardial dysfunction in sepsis Methodology: First, we observed the effects of DADLE immediately or 4h later treatment on the survival rate of endotoxemic mice. Then, we studied the dynamic changes of autophagy and mitophagy in myocardial during sepsis. Futuremore, septic mice were treated with DADLE, opioid receptor agonist antagonist Naltrindole and their co-treatment, the level of cTnI and mitochondrial membrane potential (MMP) were evaluated. At the same time, the level of mitophagy were detected by Western blot and Transmission electron microscopic. Results:.Both immediately or post-treatment with DADLE could improve the survival rate of endotoxemic mice. The level of autophagy and mitophagy reached a peak at 6h and 12h respectively,and then gradually decreased. In addition, DADLE could reduce the level of cTnI and revert the level of MMP decreasement. The level of autophagy and mitophagy were significantly increased with DADLE treatment. Conclusion: The autophagy stress induced by LPS treatment is probably happens earlier in myocardial mitochondria. DADLE could improve the survival and protect myocardial dysfunction in endotoxemic mice.It was related to the increase of autophagy and mitophagy.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"236 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123984575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Fernández-Moreno, T. Hermida-Gómez, M. J. Sánchez-Dopico, A. Dalmao-Fernández, I. Rego-Pérez, E. Cortés-Pereira, S. Relaño-Fernandez, F. Blanco-García
{"title":"Generating Rho-0 Cells using Human Mesenchymal Stem Cell Lines","authors":"M. Fernández-Moreno, T. Hermida-Gómez, M. J. Sánchez-Dopico, A. Dalmao-Fernández, I. Rego-Pérez, E. Cortés-Pereira, S. Relaño-Fernandez, F. Blanco-García","doi":"10.18143/JWMS_V2I2_1901","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1901","url":null,"abstract":"Introduction: Rho-0 generation requires immortalization process or selecting tumor cells, following by culture in presence of EtBr. The aim of this work was generate Rho-0 cells using human MSC (hMSC) lines and reagents with the ability to remove the mtDNA in a more safety way than EtBr. Methodology: Immortalized hMSCs (3a6) was used and 143B.TK-Rho-0 like control. mtDNA content was measured by RT-PCR and IF. 3a6Rho-0 was evaluated by phenotypic characterization, ROS production, Apoptotic levels and Δψm by flow cytometry and mitochondrial respiration was evaluated using a SeaHorse. Differentiation capacity was evaluated by comparing gene expression of genes involved in, adipogenesis osteogenesis and chondrogenesis. Results: The results showed 3a6 capacity to deplete their mtDNA and survive in presence of uridine. Phenotypic characterization demonstrated that 3a6Rho-0 showed a cell-surface receptor pattern typical of MSC. The functional analysis reflected that 3a6Rho-0 has similar behavior that 143B.TK-Rho-0. 3a6Rho-0 has adipogenic capacity, but lower osteogenic and chondrogenic capacity that 3a6-wt. Conclusion: We suggest that d4t is the best option to get Rho-0 cells from hMSC. Rho-0 cells obtained have similar response that typical Rho-0 used in the literature, and our cell line can be used to study the role of mitochondria in hMSC differentiation.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"389 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127951402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wanvisa Udomsinprasert, S. Honsawek, Y. Poovorawan
{"title":"Reduced leukocyte mitochondrial DNA copy number is associated with relative telomere length and oxidative DNA damage in biliary atresia patients","authors":"Wanvisa Udomsinprasert, S. Honsawek, Y. Poovorawan","doi":"10.18143/JWMS_V2I2_1890","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1890","url":null,"abstract":"Objective: Mitochondrial dysfunction has been shown to be involved in the pathophysiology of biliary atresia (BA); however, the mechanism has yet to be elucidated. There has been no study regarding the possible relationships between relative telomere length, oxidative DNA damage in the form of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and mitochondrial function in BA patients. We therefore investigated associations between mitochondrial DNA (mtDNA) copy number, relative telomere length, and 8-OHdG in peripheral blood leukocytes of BA patients. Methods: A total of 228 subjects (114 BA patients and 114 age-matched healthy controls) were enrolled in this case-control study. The mtDNA copy number, relative telomere length, and plasma 8-OHdG were measured. Results: The mtDNA copy number was significantly lower in BA patients than controls (p=0.0015). Furthermore, short telomere length and elevated plasma 8-OHdG were observed in BA patients (p<0.0001). Stratified analysis showed that mtDNA copy number was inversely associated with relative telomere length in BA patients (r=-0.49, p<0.0001), whereas mtDNA copy number in BA children revealed a positive correlation with 8-OHdG (r=0.31, p=0.001). Additionally, there was a negative correlation between mtDNA copy number and age in BA patients (r=-0.32, p=0.001). Conclusions: Decreased mtDNA copy number in BA patients was associated with relative telomere length and plasma 8-OHdG. These findings suggest that mtDNA copy number could be used as a biomarker for predicting cellular damage in post-operative BA patients; however, the prognostic role of mtDNA copy number in BA remains to be established in a longitudinal study.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125896108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial miRNA profiling in db/db mice heart","authors":"Huaping Li, Chen Chen, Daowen Wang","doi":"10.18143/JWMS_V2I2_1903","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1903","url":null,"abstract":"Background: Excessive reactive oxygen species (ROS) generated in the mitochondria is known to be a causal event in diabetic cardiomyopathy. Multiple recent studies suggest that nuclear genome-encoded miRNAs are able to translocate to the mitochondria to modulate mitochondrial activities(1,2), but the medical significance of such new miRNA function has remained unclear. Methods and Results: We observed a marked reduction of the 13 mitochondrial genes in the heart of db/db mice compared with C57 controls. Down-regulation of mitochondrial genes by siRNA recaptured some key disease features, including elevated ROS production. Microarray revealed that 34 miRNAs were upregulated and 90 miRNAs were downregulated in mitochondria of db/db heart. Through computational prediction, we found that each downregulated miRNA targeted an average of 4.9 mitochondrial genes, while each upregulated miRNA targeted an average of 2.9 mitochondrial genes. Re-expression of downregulated miRNAs into H9c2 cells led to enhanced mitochondrial genes translation and reduced ROS production. Conclusions: Our findings suggest that reduced mitochondrial miRNAs in db/db heart contribute to impaired mitochondrial genes expression and elevated ROS production. Re-expression of downregulated miRNAs enhances mitochondrial translation, which is sufficient to reduce ROS production. This observation suggests a novel theoretical ground for developing miRNA-based therapeutics against diabetic cardiomyopathy.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116175030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evelina Rekuvienė, L. Ivanovienė, V. Borutaite, R. Morkūnienė
{"title":"Anesthesia of pentobarbital protects against ischemia induced cell death and rat cortex and cerebellum mitochondrial damage","authors":"Evelina Rekuvienė, L. Ivanovienė, V. Borutaite, R. Morkūnienė","doi":"10.18143/JWMS_V2I2_1891","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1891","url":null,"abstract":"Aim: To investigate the effect of pentobarbital on respiration, calcium induced- mitochondrial permeability transition pore (mPTP) opening of isolated rat brain cortex and cerebellum mitochondria and infarct volume and cell death after 120 min. ischemia in rats. Methods: Brains of adult Wistar male rats were exposed to 120 min. ischemia with/without pentobarbital 40 mg/kg (Dolethal). Respiration of isolated cortical and cerebellar mitochondria was measured oxygraphically using a Oroboros instrument. Ca2+-induced mPTP opening as calcium retention capacity (CRC) was measured using fluorescent dye Calcium Green 5N. Infarct volume was assessed in brain sections of 1 mm thick stained by 2% triphenyl-tetrazolium chloride (TTC). To determine cell death in brain slices of 100 µm was used double fluorescent staining by propidium iodide (PI) and Hoechst. Results: Brain ischemia significantly decreased resistance of isolated cortex and cerebellum mitochondria to calcium-induced mPTP opening and inhibited respiration rate in state 3 with both substrates pyruvate plus malate and succinate. However, pentobarbital before ischemia re-established CRC of both, cortex and cerebellum mitochondria to control level. Pentobarbital also protected against ischemia-induced inhibition of state 3 respiration with pyruvate plus malate and succinate of cortex mitochondria and cerebellum mitochondria only with succinate, while state 3 respiration of cerebellum mitochondria with pyruvate and malate was not changed. Anesthesia with dolethal before ischemia significantly decreased infarct volume and cell death of rat brain after 120 min ischemia. Conclusions: These results demonstrate that anesthesia by pentobarbital protects brain cells against 120 min ischemia-induced cell death reducing inhibition of mitochondrial respiration and sensitivity to calcium-induced mPTP opening.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116641624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria – a switch board between various cell death modalities","authors":"V. Gogvadze, S. Orrenius, B. Zhivotovsky","doi":"10.18143/JWMS_V2I1.966","DOIUrl":"https://doi.org/10.18143/JWMS_V2I1.966","url":null,"abstract":"For many years, mitochondria were regarded exclusively as cellular power plants, destined to provide the cell with energy in the form of ATP. Mitochondrial deterioration can have fatal consequences for cellular physiology and be a cause of various diseases. Subsequent studies revealed the involvement of mitochondria in the regulation and execution of multiple modalities of cell death. Analysis of the involvement of mitochondria in the control of various modes of cell death led to the conclusion that mitochondria might play a leading role as a “switch-board” between various cell death modalities.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124840642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial Function and Metabolic States: On the Differences between Brain In Vitro and In Vivo Conditions and Monitoring","authors":"A. Mayevsky","doi":"10.18143/JWMS_V2I1.955","DOIUrl":"https://doi.org/10.18143/JWMS_V2I1.955","url":null,"abstract":"Although mitochondria were discovered more than 150 years ago, monitoring of mitochondrial function in-patients in real time and in vivo is very rare. In most of the studies published in this field, isolated mitochondria or isolated cells in vitro were and are in use and therefore the technology used in those studies cannot be adapted to patient monitoring. Evaluation of mitochondrial function by optical monitoring of NADH redox state could be used in isolated mitochondria as well as in patients under various clinical situations. Therefore, we developed a medical device that could provide real time data on mitochondrial function as well as microcirculatory blood flow and oxygenation using optical based technology. In order to improve, significantly, outcome of patients in critical care medicine and other conditions it is necessary to adapt our device that was cleared by the FDA. Our preliminary results in patients indicate that our approach of monitoring of tissue vitality is the next step in improving the health of humankind.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"25 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113979226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}