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Mitochondria AND NAD ratio

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https://www.readbyqxmd.com/read/28628905/a-ros-mediated-mitochondrial-pathway-and-nrf2-pathway-activation-are-involved-in-bde-47-induced-apoptosis-in-neuro-2a-cells
#1
Hongmei Chen, Xuexi Tang, Bin Zhou, Zhongyuan Zhou, Ningning Xu, You Wang
Our previous study showed that 2,2'-,4,4'-tetrabromodiphenyl ether (BDE-47) is cytotoxic and induces apoptosis in Neuro-2a cells. In the present study, we aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcriptional regulator of oxidative stress and apoptosis, is involved in this process. The results of toxicological experiments showed that BDE-47 decreased the cellular mitochondrial membrane potential (MMP) and increased cytochrome c release to the cytoplasm, followed by an increase in intracellular caspase-9 and caspase-3 activity, suggesting that a mitochondrial pathway was involved in the apoptotic process...
June 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28554565/antioxidant-mechanism-of-mitochondria-targeted-plastoquinone-skq1-is-suppressed-in-aglycemic-hepg2-cells-dependent-on-oxidative-phosphorylation
#2
Jan Ježek, Hana Engstová, Petr Ježek
Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anaemia-cells-to-glycolytic-metabolism
#3
Enrico Cappelli, Paola Cuccarolo, Giorgia Stroppiana, Maurizio Miano, Roberta Bottega, Vanessa Cossu, Paolo Degan, Silvia Ravera
Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#4
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tricarboxylic-acid-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#5
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, Michael Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28035366/inhibitory-effects-of-alpha-lipoic-acid-on-oxidative-stress-in-the-rostral-ventrolateral-medulla-in-rats-with-salt-induced-hypertension
#6
Yu-Peng Huang, Hong-Yan Jin, Hui-Ping Yu
Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alpha‑lipoic acid (ALA) is widely recognized for its potent superoxide inhibitory properties, and it can safely penetrate deep into the brain. The aim of this study was to explore whether ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the NAD(P)H oxidase (NOX)-derived overproduction of reactive oxygen species (ROS) in the mitochondria in the RVLM, and thus attenuating the development of salt‑induced hypertension...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28003863/resolving-contributions-of-oxygen-consuming-and-ros-generating-enzymes-at-the-synapse
#7
COMPARATIVE STUDY
Engy A Abdel-Rahman, Ali M Mahmoud, Abdullah Aaliya, Yasmine Radwan, Basma Yasseen, Abdelrahman Al-Okda, Ahmed Atwa, Eslam Elhanafy, Moaaz Habashy, Sameh S Ali
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27867097/mitochondrial-remodeling-in-the-liver-following-chronic-alcohol-feeding-to-rats
#8
Derick Han, Heather S Johnson, Madhuri P Rao, Gary Martin, Harsh Sancheti, Kai H Silkwood, Carl W Decker, Kim Tho Nguyen, Joseph G Casian, Enrique Cadenas, Neil Kaplowitz
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#9
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27634671/pharmacological-inhibition-of-nox4-ameliorates-alcohol-induced-liver-injury-in-mice-through-improving-oxidative-stress-and-mitochondrial-function
#10
Qian Sun, Wenliang Zhang, Wei Zhong, Xinguo Sun, Zhanxiang Zhou
BACKGROUND: Oxidative stress plays a crucial role in the development of alcoholic liver disease (ALD), however effective pharmacological treatment for oxidative injury is still lacking. The objective of this study was to determine whether inhibition of NADPH oxidase activity could reverse alcohol-induced liver injury via protecting mitochondrial functions. METHODS: C57BL/6J mice were pair-fed with Lieber-DeCarli control or ethanol diet for four week with or without administration with 30mg/kg/d GKT137831, a NOX4 inhibitor for the last two weeks...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27558544/hyperammonaemia-induced-skeletal-muscle-mitochondrial-dysfunction-results-in-cataplerosis-and-oxidative-stress
#11
Gangarao Davuluri, Allawy Allawy, Samjhana Thapaliya, Julie H Rennison, Dharmvir Singh, Avinash Kumar, Yana Sandlers, David R Van Wagoner, Chris A Flask, Charles Hoppel, Takhar Kasumov, Srinivasan Dasarathy
KEY POINTS: Hyperammonaemia occurs in hepatic, cardiac and pulmonary diseases with increased muscle concentration of ammonia. We found that ammonia results in reduced skeletal muscle mitochondrial respiration, electron transport chain complex I dysfunction, as well as lower NAD(+) /NADH ratio and ATP content. During hyperammonaemia, leak of electrons from complex III results in oxidative modification of proteins and lipids. Tricarboxylic acid cycle intermediates are decreased during hyperammonaemia, and providing a cell-permeable ester of αKG reversed the lower TCA cycle intermediate concentrations and increased ATP content...
December 15, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27551320/moderately-decreased-maternal-dietary-energy-intake-during-pregnancy-reduces-fetal-skeletal-muscle-mitochondrial-biogenesis-in-the-pigs
#12
Tiande Zou, Bing Yu, Jie Yu, Xiangbing Mao, Ping Zheng, Jun He, Zhiqing Huang, Yue Liu, Daiwen Chen
BACKGROUND: Mitochondria are of major importance in oocyte and early embryo, playing a key role in maintaining energy homeostasis. Epidemiological findings indicate that maternal undernutrition-induced mitochondrial dysfunction during pregnancy is associated with the development of metabolic disorders in offspring. Here, we investigated the effects of moderately decreased maternal energy intake during pregnancy on skeletal muscle mitochondrial biogenesis in fetal offspring with pig as a model...
2016: Genes & Nutrition
https://www.readbyqxmd.com/read/27489254/normalization-of-nad-redox-balance-as-a-therapy-for-heart-failure
#13
Chi Fung Lee, Juan D Chavez, Lorena Garcia-Menendez, Yongseon Choi, Nathan D Roe, Ying Ann Chiao, John S Edgar, Young Ah Goo, David R Goodlett, James E Bruce, Rong Tian
BACKGROUND: Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. METHODS: We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites...
September 20, 2016: Circulation
https://www.readbyqxmd.com/read/27474736/the-contribution-of-nicotinamide-nucleotide-transhydrogenase-to-peroxide-detoxification-is-dependent-on-the-respiratory-state-and-counterbalanced-by-other-sources-of-nadph-in-liver-mitochondria
#14
Juliana Aparecida Ronchi, Annelise Francisco, Luiz Augusto Correa Passos, Tiago Rezende Figueira, Roger Frigério Castilho
The forward reaction of nicotinamide nucleotide transhydrogenase (NNT) reduces NADP(+) at the expense of NADH oxidation and H(+) movement down the electrochemical potential across the inner mitochondrial membrane, establishing an NADPH/NADP(+) ratio severalfold higher than the NADH/NAD(+) ratio in the matrix. In turn, NADPH drives processes, such as peroxide detoxification and reductive biosynthesis. In this study, we generated a congenic mouse model carrying a mutated Nnt(C57BL/6J) allele from the C57BL/6J substrain...
September 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27337687/autophagy-deficiency-in-myeloid-cells-increases-susceptibility-to-obesity-induced-diabetes-and-experimental-colitis
#15
Hae-Youn Lee, Jinyoung Kim, Wenying Quan, June-Chul Lee, Min-Soo Kim, Seok-Hyung Kim, Jin-Woo Bae, Kyu Yeon Hur, Myung-Shik Lee
Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue...
August 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27298826/oxidative-stress-and-liver-morphology-in-experimental-cyclosporine-a-induced-hepatotoxicity
#16
Agnieszka Korolczuk, Kinga Caban, Magdalena Amarowicz, Grażyna Czechowska, Joanna Irla-Miduch
Cyclosporine A is an immunosuppressive drug used after organ's transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat's hepatocytes. Male Wistar rats were used: group A (control) receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27183225/cyclophilin-d-knock-out-mice-show-enhanced-resistance-to-osteoporosis-and-to-metabolic-changes-observed-in-aging-bone
#17
Laura C Shum, Noelle S White, Sergiy M Nadtochiy, Karen L de Mesy Bentley, Paul S Brookes, Jennifer H Jonason, Roman A Eliseev
Pathogenic factors associated with aging, such as oxidative stress and hormone depletion converge on mitochondria and impair their function via opening of the mitochondrial permeability transition pore (MPTP). The MPTP is a large non-selective pore regulated by cyclophilin D (CypD) that disrupts mitochondrial membrane integrity. MPTP involvement has been firmly established in degenerative processes in heart, brain, and muscle. Bone has high energy demands and is therefore expected to be highly sensitive to mitochondrial dysfunction...
2016: PloS One
https://www.readbyqxmd.com/read/27157912/malate-aspartate-shuttle-inhibitor-aminooxyacetic-acid-leads-to-decreased-intracellular-atp-levels-and-altered-cell-cycle-of-c6-glioma-cells-by-inhibiting-glycolysis
#18
Caixia Wang, Heyu Chen, Mingchao Zhang, Jie Zhang, Xunbin Wei, Weihai Ying
NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures...
August 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27155879/the-non-apoptotic-action-of-bcl-xl-regulating-ca-2-signaling-and-bioenergetics-at-the-er-mitochondrion-interface
#19
Abasha Williams, Teruo Hayashi, Daniel Wolozny, Bojiao Yin, Tzu-Chieh Su, Michael J Betenbaugh, Tsung-Ping Su
Bcl-2 family proteins are known to competitively regulate Ca(2+); however, the specific inter-organelle signaling pathways and related cellular functions are not fully elucidated. In this study, a portion of Bcl-xL was detected at the ER-mitochondrion interface or MAM (mitochondria-associated ER membrane) in association with type 3 inositol 1,4,5-trisphosphate receptors (IP3R3); an association facilitated by the BH4 and transmembrane domains of Bcl-xL. Moreover, increasing Bcl-xL expression enhanced transient mitochondrial Ca(2+) levels upon ER Ca(2+) depletion induced by short-term, non-apoptotic incubation with thapsigargin (Tg), while concomitantly reducing cytosolic Ca(2+) release...
June 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27124460/complementation-of-mitochondrial-electron-transport-chain-by-manipulation-of-the-nad-nadh-ratio
#20
Denis V Titov, Valentin Cracan, Russell P Goodman, Jun Peng, Zenon Grabarek, Vamsi K Mootha
A decline in electron transport chain (ETC) activity is associated with many human diseases. Although diminished mitochondrial adenosine triphosphate production is recognized as a source of pathology, the contribution of the associated reduction in the ratio of the amount of oxidized nicotinamide adenine dinucleotide (NAD(+)) to that of its reduced form (NADH) is less clear. We used a water-forming NADH oxidase from Lactobacillus brevis (LbNOX) as a genetic tool for inducing a compartment-specific increase of the NAD(+)/NADH ratio in human cells...
April 8, 2016: Science
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