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Hazel H Szeto, Shaoyi Liu, Yi Soong, Nazia Alam, Glen T Prusky, Surya V Seshan
Obesity is a major risk factor for the development of chronic kidney disease, even independent of its association with hypertension, diabetes, and dyslipidemia. The primary pathologic finding of obesity-related kidney disease is glomerulopathy, with glomerular hypertrophy, mesangial matrix expansion, and focal segmental glomerulosclerosis. Proposed mechanisms leading to renal pathology include abnormal lipid metabolism, lipotoxicity, inhibition of AMP kinase, and endoplasmic reticulum stress. Here we report dramatic changes in mitochondrial structure in glomerular endothelial cells, podocytes, and proximal tubular epithelial cells after 28 weeks of a high-fat diet in C57BL/6 mice...
November 2016: Kidney International
Yu Pang, Chao Wang, Ling Yu
Glaucoma is the second leading cause of irreversible blindness and a neurodegenerative disease with a complex pathogenesis. Increasing evidence suggests that oxidative stress and mitochondrial dysfunction have crucial roles in most neurodegenerative diseases such as glaucoma. The conventional clinical treatment for glaucoma is lowering the intraocular pressure (IOP). Some patients have normal IOP, whereas other patients appear to obtain adequate control of IOP after filtration surgery or medication. However, these patients still experience progressive visual field loss...
2015: Medical Hypothesis, Discovery and Innovation in Ophthalmology
M C W Schoenell, C L Alberton, C L Tiggemann, M Noll, R Costa, N S Santos, L F M Kruel
This study aims to analyze the neuromuscular adaptations of sedentary young women between water-based resistance training performed with single and multiple sets. 66 women (24.72±4.33 years old) were randomly divided into 2 training groups: SS (single set of 30 s) and MS (3 sets of 30 s). Both groups performed 2 sessions per week for 10 weeks. One repetition maximal test (1RM), muscle endurance test (maximal repetitions at 60% 1RM) and muscle power test (squat and countermovement jump performance) were evaluated at pre- and post-training...
September 2016: International Journal of Sports Medicine
Leonie G M Wijermars, Alexander F Schaapherder, Dorottya K de Vries, Lars Verschuren, Rob C I Wüst, Sarantos Kostidis, Oleg A Mayboroda, Frans Prins, Jan Ringers, Jörgen Bierau, Jaap A Bakker, Teake Kooistra, Jan H N Lindeman
Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF...
July 2016: Kidney International
Jae Hyo Park, Gil Su Jang, Hyung Yoon Kim, Ki Hwan Seok, Hee Jae Chae, Sol Kyu Lee, Seung Ki Joo
Realizing a low-temperature polycrystalline-silicon (LTPS) thin-film transistor (TFT) with sub-kT/q subthreshold slope (SS) is significantly important to the development of next generation active-matrix organic-light emitting diode displays. This is the first time a sub-kT/q SS (31.44 mV/dec) incorporated with a LTPS-TFT with polycrystalline-Pb(Zr,Ti)O3 (PZT)/ZrTiO4 (ZTO) gate dielectrics has been demonstrated. The sub-kT/q SS was observed in the weak inversion region at -0.5 V showing ultra-low operating voltage with the highest mobility (250...
2016: Scientific Reports
Hung-I Lu, Tien-Hung Huang, Pei-Hsun Sung, Yung-Lung Chen, Sarah Chua, Han-Yan Chai, Sheng-Ying Chung, Chu-Feng Liu, Cheuk-Kwan Sun, Hsueh-Wen Chang, Yen-Yi Zhen, Fan-Yen Lee, Hon-Kan Yip
AIM: Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. METHODS: Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d...
May 2016: Acta Pharmacologica Sinica
Jing Wu, Mingqiang Zhang, Huihui Li, Xiaoru Sun, Shuangying Hao, Muhuo Ji, Jianjun Yang, Kuanyu Li
Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation...
May 15, 2016: Behavioural Brain Research
Yanjuan Hou, Shuangcheng Li, Ming Wu, Jinying Wei, Yunzhuo Ren, Chunyang Du, Haijiang Wu, Caili Han, Huijun Duan, Yonghong Shi
Oxidative stress is implicated in the pathogenesis of diabetic kidney injury. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge reactive oxygen species (ROS). Here, we investigated the effect and molecular mechanism of mitochondria-targeted antioxidant peptide SS-31 on injuries in diabetic kidneys and mouse mesangial cells (MMCs) exposed to high-glucose (HG) ambience. CD-1 mice underwent uninephrectomy and streptozotocin treatment prior to receiving daily intraperitoneal injection of SS-31 for 8 wk...
March 15, 2016: American Journal of Physiology. Renal Physiology
Caterina Constantinou, Yiorgos Apidianakis, Nikolaos Psychogios, Valeria Righi, Michael N Mindrinos, Nadeem Khan, Harold M Swartz, Hazel H Szeto, Ronald G Tompkins, Laurence G Rahme, A Aria Tzika
Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of genes in Drosophila melanogaster, a useful model for investigating genetics and physiology. After trauma was induced by a non-lethal needle puncture of the thorax, we observed the differential expression of genes encoding for mitochondrial uncoupling proteins, as well as those encoding for apoptosis-related and insulin signaling-related proteins, thus indicating muscle functional dysregulation...
February 2016: International Journal of Molecular Medicine
Shuangying Hao, Jiajie Ji, Hongting Zhao, Longcheng Shang, Jing Wu, Huihui Li, Tong Qiao, Kuanyu Li
Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264...
2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jing Wu, Huihui Li, Xiaoru Sun, Hui Zhang, Shuangying Hao, Muhuo Ji, Jianjun Yang, Kuanyu Li
Isoflurane possesses neurotoxicity and can induce cognitive deficits, particularly in aging mammals. Mitochondrial reactive oxygen species (mtROS) have been linked to the early pathogenesis of this disorder. However, the role of mtROS remains to be evaluated due to a lack of targeted method to treat mtROS. Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic. We further investigated the possible mechanisms underlying the effects of SS-31 on hippocampal neuro-inflammation and apoptosis...
2015: PloS One
Adam P Lightfoot, Giorgos K Sakellariou, Gareth A Nye, Francis McArdle, Malcolm J Jackson, Richard D Griffiths, Anne McArdle
TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the mitochondrial generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the effect of TNF-α on the production of myokines by skeletal muscle. Significant increases were seen in the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of cytokines by muscle cells. An increase was also seen in superoxide in response to treatment with TNF-α, which was localised to the mitochondria and this was also associated with activation of NF-κB...
December 2015: Redox Biology
Alexander G Nickel, Albrecht von Hardenberg, Mathias Hohl, Joachim R Löffler, Michael Kohlhaas, Janne Becker, Jan-Christian Reil, Andrey Kazakov, Julia Bonnekoh, Moritz Stadelmaier, Sarah-Lena Puhl, Michael Wagner, Ivan Bogeski, Sonia Cortassa, Reinhard Kappl, Bastian Pasieka, Michael Lafontaine, C Roy D Lancaster, Thomas S Blacker, Andrew R Hall, Michael R Duchen, Lars Kästner, Peter Lipp, Tanja Zeller, Christian Müller, Andreas Knopp, Ulrich Laufs, Michael Böhm, Markus Hoth, Christoph Maack
Mitochondrial reactive oxygen species (ROS) play a central role in most aging-related diseases. ROS are produced at the respiratory chain that demands NADH for electron transport and are eliminated by enzymes that require NADPH. The nicotinamide nucleotide transhydrogenase (Nnt) is considered a key antioxidative enzyme based on its ability to regenerate NADPH from NADH. Here, we show that pathological metabolic demand reverses the direction of the Nnt, consuming NADPH to support NADH and ATP production, but at the cost of NADPH-linked antioxidative capacity...
September 1, 2015: Cell Metabolism
Camila Nunes Carvalho, Rodrigo Feliciano do Carmo, Angela Luzia Pinto Duarte, Alessandra Albuquerque Tavares Carvalho, Jair Carneiro Leão, Luiz Alcino Gueiros
OBJECTIVE: The aim of this study was to evaluate the influence of Th17 polymorphisms on the susceptibility or severity of rheumatoid arthritis (RA) and Sjögren's syndrome (SS). MATERIALS AND METHODS: The study sample comprised 206 individuals of both genders divided into three groups: exclusive rheumatoid arthritis (RA-100 patients), rheumatoid arthritis and Sjögren's syndrome (RA/SS-31 patients), and healthy controls (C-75 individuals). All the individuals were submitted to clinical evaluation, unstimulated sialometry, and Schirmer test; some patients with RA were also submitted to minor salivary gland biopsy for definition of SS diagnosis...
April 2016: Clinical Oral Investigations
Guoming Li, Jing Wu, Renqi Li, Dong Yuan, Yunxia Fan, Jianjun Yang, Muhuo Ji, Sihai Zhu
Oxidative stress causes mitochondrial impairment, the failure of energy production, and consequent organ dysfunctions. The aim of the present study was to investigate the potential therapeutic effects of mitochondrial antioxidant SS-31 on sepsis-induced organ dysfunctions and to explore the possible mechanism. Sepsis was induced by cecal ligation and puncture. Immediately and at 5 h after the operation, SS-31 (5 mg/kg) or vehicle was administered intraperitoneally. The levels of organ dysfunctions, malondialdehyde, superoxide dismutase, proinflammatory cytokines, pulmonary wet-to-dry weight ratio, myeloperoxidase activity, histological scores, nuclear factor kappa B p65, inducible nitric oxide synthase, reactive oxygen species, adenosine triphosphate, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were assessed at the indicated time points...
February 2016: Inflammation
Carmine Pasquale Cerrato, Marco Pirisinu, Efstathios Nikolaos Vlachos, Ülo Langel
Cell-penetrating peptides (CPPs) are short, nontoxic peptides with cationic and/or amphipathic properties able to cross the cellular membrane. CPPs are used for the delivery of a wide variety of cargoes, such as proteins, oligonucleotides, and therapeutic molecules. The aim of the present study was to synthesize unusually small novel CPPs targeting mitochondria based on the Szeto-Schiller peptide (SS-31) to influence intramitochondrial processes and to improve the biologic effects. All the peptides used were synthesized manually using 9-fluorenylmethyloxycarbonyl chemistry...
November 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wei Ma, Xiaobo Zhu, Xiaoyan Ding, Tao Li, Yijun Hu, Xuting Hu, Lin Yuan, Lei Lei, Andina Hu, Yan Luo, Shibo Tang
The present study aimed to investigate the ability of SS31, a novel mitochondria‑targeted peptide to protect against t‑BHP‑induced mitochondrial dysfunction and apoptosis in 661W cell lines. The 661W cells were treated with various concentrations of SS‑31 and an MTT assay was used to determine cell viability. The expression of nitrotyrosine and 8‑hydroxydeoxyguanosine (8‑OHdG) was detected using immunofluorescent staining. Apoptosis were assessed using Hoechst staining and an annexin V/propidium iodide flow cytometer...
October 2015: Molecular Medicine Reports
Arthur J Cheng, Joseph D Bruton, Johanna T Lanner, Håkan Westerblad
The contractile performance of skeletal muscle declines during intense activities, i.e. fatigue develops. Fatigued muscle can enter a state of prolonged low-frequency force depression (PLFFD). PLFFD can be due to decreased tetanic free cytosolic [Ca(2+) ] ([Ca(2+) ]i ) and/or decreased myofibrillar Ca(2+) sensitivity. Increases in reactive oxygen and nitrogen species (ROS/RNS) may contribute to fatigue-induced force reductions. We studied whether pharmacological ROS/RNS inhibition delays fatigue and/or counteracts the development of PLFFD...
January 15, 2015: Journal of Physiology
Arthur J Cheng, Joseph D Bruton, Johanna T Lanner, Håkan Westerblad
The contractile performance of skeletal muscle declines during intense activities, i.e. fatigue develops. Fatigued muscle can enter a state of prolonged low-frequency force depression (PLFFD). PLFFD can be due to decreased tetanic free cytosolic [Ca(2+)] ([Ca(2+)]i) and/or decreased myofibrillar Ca(2+) sensitivity. Increases in reactive oxygen and nitrogen species (ROS/RNS) may contribute to fatigue-induced force reductions. We studied whether pharmacological ROS/RNS inhibition delays fatigue and/or counteracts the development of PLFFD...
November 14, 2014: Journal of Physiology
Thekkuttuparambil Ananthanarayanan Ajith, Thankamani Gopinathan Jayakumar
Mitochondria are one of the major sites for the generation of reactive oxygen species (ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dysfunction of mitochondria increase the risk for a large number of human diseases, including cardiovascular diseases (CVDs). Heart failure (HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the CVDs in which the role of mitochondrial oxidative stress has been reported...
October 26, 2014: World Journal of Cardiology
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