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Cellular respiration

Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
Himalee S Sabnis, Heath L Bradley, Shweta Tripathi, Wen-Mei Yu, William Tse, Cheng-Kui Qu, Kevin D Bunting
Current therapy for acute myeloid leukemia (AML) primarily includes high-dose cytotoxic chemotherapy with or without allogeneic stem cell transplantation. Targeting unique cellular metabolism of cancer cells is a potentially less toxic approach. Monotherapy with mitochondrial inhibitors like metformin have met with limited success since escape mechanisms such as increased glycolytic ATP production, especially in hyperglycemia, can overcome the metabolic blockade. As an alternative strategy for metformin therapy, we hypothesized that the combination of 6-benzylthioinosine (6-BT), a broad-spectrum metabolic inhibitor, and metformin could block this drug resistance mechanism...
October 5, 2016: Leukemia Research
Gargi Mahapatra, Ashwathy Varughese, Qinqin Ji, Icksoo Lee, Jenney Liu, Asmita Vaishnav, Christopher Sinkler, Alexandr A Kapralov, Carlos T Moraes, Thomas H Sanderson, Timothy L Stemmler, Lawrence I Grossman, Valerian E Kagan, Joseph S Brunzelle, Arthur R Salomon, Brian F P Edwards, Maik Hüttemann
Mammalian cytochrome c (Cytc) plays a key role in cellular life and death decisions, functioning as an electron carrier in the electron transport chain (ETC) and as a trigger of apoptosis when released from the mitochondria. However, its regulation is not well understood. We show that the major fraction of Cytc isolated from kidneys is phosphorylated on Thr28, leading to a partial inhibition of respiration in the reaction with cytochrome c oxidase. To further study the effect of Cytc phosphorylation in vitro, we generated Thr28Glu phosphomimetic Cytc, revealing superior behavior regarding protein stability and its ability to degrade reactive oxygen species compared to wild-type unphosphorylated Cytc...
October 7, 2016: Journal of Biological Chemistry
Jody K Takemoto, Tracie L Miller, Jiajia Wang, Denise L Jacobson, Mitchell E Geffner, Russell B Van Dyke, Mariana Gerschenson
OBJECTIVE: To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected (pHIV) youth. DESIGN: Case-control study METHODS:: Mitochondrial respiration was assessed in pHIV youth in Tanner stages 2-5, 25 youth with IR (IR+) and 50 without IR (IR-) who were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS). IR was defined as a Homeostatic Model of Assessment for Insulin Resistance (HOMA-IR) value ≥4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells...
October 14, 2016: AIDS
Jason J Rose, Ling Wang, Qinzi Xu, Charles F McTiernan, Sruti Shiva, Jesus Tejero, Mark T Gladwin
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1-3%. A significant number of patients who survive CO poisoning suffer from long term neurologic and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels, but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation and free radical generation, especially in the brain and heart...
October 18, 2016: American Journal of Respiratory and Critical Care Medicine
Me-Hea Park
The high metabolic rate of harvested asparagus spears (Asparagus officinalis L.) causes rapid deterioration. To extend shelf life, we investigated the effect of sucrose treatment on asparagus during storage. Asparagus spears were treated with 3%, 5%, and 10% sucrose and stored at 2 °C for 20 h. Cellular respiration decreased, but other processes were unaltered by exogenous sucrose. The overall appearance of asparagus treated with 3% sucrose and stored at 2 °C for 18 days was rated as good and excellent, unlike that of untreated spears...
October 14, 2016: Biochemical and Biophysical Research Communications
Jian-Jun Wen, Xianxiu Wan, John Thacker, Nisha Jain Garg
BACKGROUND: Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM. METHODS AND RESULTS: C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post-infection), treated with sildenafil (SIL, 1 mg/kg) twice per week for 3 weeks...
June 2016: JACC. Basic to Translational Science
Jenny M Pedersen, Yoo-Sik Shim, Vaibhav Hans, Martin B Phillips, Jeffrey M Macdonald, Glenn Walker, Melvin E Andersen, Harvey J Clewell, Miyoung Yoon
Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results...
2016: Frontiers in Bioengineering and Biotechnology
Runyu Guo, Jinke Gu, Meng Wu, Maojun Yang
Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indispensable biological process in almost all living creatures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by Yang's group from Tsinghua University (Gu et al. Nature 237(7622):639-643, 2016) firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening...
October 14, 2016: Protein & Cell
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms are unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD+/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
October 14, 2016: Journal of Neurochemistry
Jonathan C Jun, Ronald Devera, Dileep Unnikrishnan, Mi-Kyung Shin, Shannon Bevans-Fonti, Qiaoling Yao, Aman Rathore, Haris Younas, Nils Halberg, Philipp E Scherer, Vsevolod Y Polotsky
: Hypoxia-inducible factor-1α (HIF-1α) in adipose tissue is known to promote obesity. We hypothesized that HIF-1α interferes with brown fat thermogenesis, thus decreasing energy expenditure. To test this hypothesis, we compared transgenic mice constitutively expressing HIF-1α in adipose tissues (HIF-1α++) at usual temperature (22 °C), where brown fat is somewhat active, or at thermoneutrality (30 °C), where brown fat is minimally active. HIF-1α++ mice or control litter mates were separated into room temperature (22 °C) or thermoneutrality (30 °C) groups...
October 14, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Bhabatosh Banik, Brett W Askins, Shanta Dhar
The field of intracellular organelle targeting using nanoparticle (NP) is mushrooming rapidly. Thus, the area of nanotechnology-enabled targeting of mitochondrion, the cellular powerhouse, for diseases characterized by mitochondrial dysfunctions such as cancer, diseases of the central nervous system, and cardiovascular diseases is also growing at a rapid pace. Optimization of a NP's ability to target the mitochondria requires quantification of the particles in this subcellular organelle and isolation of mitochondria from the cells...
October 13, 2016: Nanoscale
Judith Kandel, Alessia A Angelin, Douglas C Wallace, David M Eckmann
An abundance of research suggests that cellular mitochondrial and cytoskeletal disruption are related, but few studies have directly investigated causative connections between the two. We previously demonstrated that inhibiting microtubule and microfilament polymerization affects mitochondrial motility on the whole-cell level in fibroblasts. Since mitochondrial motility can be indicative of mitochondrial function, we now further characterize the effects of these cytoskeletal inhibitors on mitochondrial potential, morphology and respiration...
October 13, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Daniel Torralba, Francesc Baixauli, Francisco Sánchez-Madrid
Mitochondria regulate multiple cell processes, including calcium signaling, apoptosis and cell metabolism. Mitochondria contain their own circular genome encoding selected subunits of the oxidative phosphorylation complexes. Recent findings reveal that, in addition to being maternally inherited, mitochondria can traverse cell boundaries and thus be horizontally transferred between cells. Although, the physiological relevance of this phenomenon is still under debate, mitochondria uptake rescues mitochondrial respiration defects in recipient cells and regulates signaling, proliferation or chemotherapy resistance in vitro and in vivo...
2016: Frontiers in Cell and Developmental Biology
Yijun Liu, Nathalie Muñoz, Ang-Chen Tsai, Timothy M Logan, Teng Ma
Spontaneous aggregation and the associated enhancement of stemness have been observed in many anchorage dependent cells. Recently, aggregation of human mesenchymal stem cells (hMSCs) in non-adherent culture has been shown to reverse expansion-induced heterogeneity and loss of stemness and reprogram the hMSC to reacquire their primitive phenotype, a phenomenon that can significantly enhance therapeutic applications of hMSC. The objective of this study was to investigate the mechanistic basis underlying the connection between multi-cellular aggregation and stemness enhancement in hMSC by testing the hypothesis that cellular events induced during 3D aggregation on non-adherent substratum induces changes in mitochondrial metabolism that promote the expression of stem cell genes Oct4, Sox2, and Nanog...
October 11, 2016: Stem Cells
Lei Xiong, Yi Tang, Zhaoyang Liu, Jing Dai, Xiaozhou Wang
PURPOSE: To understand the role of Bcl-2 overexpression in oral tongue squamous cell carcinoma (OTSCC) patients and investigate the efficacy of targeting Bcl-2 in OTSCC. METHODS: The expression level of Bcl-2 on normal tongue cells and OTSCC cells were measured by real-time PCR and western blotting. The functional roles of Bcl-2 were examined by MTS, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing mitochondrial functions in a panel of OTSCC cell lines...
2016: SpringerPlus
L W Hall, F R Dunshea, J D Allen, S Rungruang, J L Collier, N M Long, R J Collier
Betaine (BET), a natural, organic osmolyte, improves cellular efficiency by acting as a chaperone, refolding denatured proteins. To test if dietary BET reduced the effect of heat stress (HS) in lactating dairy cows, multiparous, lactating Holstein cows (n = 24) were blocked by days in milk (101.4 ± 8.6 d) and randomly assigned to 1 of 3 daily intakes of dietary BET: the control (CON) group received no BET, mid intake (MID) received 57 mg of BET/kg of body weight, and high dose (HI) received 114 mg of BET/kg of body weight...
October 5, 2016: Journal of Dairy Science
Praveen Mannam, Navin Rauniyar, TuKiet T Lam, Ruiyan Luo, Patty J Lee, Anup Srivastava
Cigarette smoking is the primary risk factor for COPD which is characterized by excessive inflammation and airflow obstruction of the lung. While inflammation is causally related to initiation and progression of COPD, the mitochondrial mechanisms that underlie the associated inflammatory responses are poorly understood. In this context, we have studied the role played by Mitogen activated protein (MAP) kinase kinase 3 (MKK3), a dual-specificity protein kinase, in cigarette smoke induced-inflammation and mitochondrial dysfunction...
October 4, 2016: Free Radical Biology & Medicine
J G Toffaletti, C R Rackley
Although part of a common "blood gas" test panel with pH and pCO2, the pO2, %O2Hb, and related parameters are independently used to detect and monitor oxygen deficits from a variety of causes. Measurement of blood gases and cooximetry may be done by laboratory analyzers, point of care testing, noninvasive pulse oximetry, and transcutaneous blood gases. The specimen type and mode of monitoring oxygenation that are chosen may be based on a combination of urgency, practicality, clinical need, and therapeutic objectives...
2016: Advances in Clinical Chemistry
Anna Czajka, Afshan N Malik
Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN), a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs) and proximal tubular cells (HK-2) were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer...
September 17, 2016: Redox Biology
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