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https://www.readbyqxmd.com/read/28717408/sirt3-enhances-mesenchymal-stem-cell-longevity-and-differentiation
#1
Ryan A Denu
Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and immunomodulatory properties as well as their osteogenic and chondrogenic capabilities. However, there are considerable interdonor variability and heterogeneity of MSC populations, making it challenging to compare different products. Furthermore, proliferation, differentiation, and immunomodulation of MSCs decrease with aging and ex vivo expansion. The sirtuins have emerged as a class of protein deacylases involved in aging, oxidative stress, and metabolism...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28715593/physical-exercise-improves-total-antioxidant-capacity-and-gene-expression-in-rat-hippocampal-tissue
#2
F Franzoni, G Federighi, J Fusi, E Cerri, R Banducci, A Petrocchi, A Innocenti, C Pruneti, S Daniele, S Pellegrini, C Martini, R Scuri, F Galetta
Exercise may exert beneficial effects on cognitive functions and play an important role in the prevention of neurodegenerative diseases. Such effects seem to be mediated by changes in anti-oxidative status, but limited information is available on the nature of molecular pathways supporting the antioxidant effects of exercise in the brain. In this study 3-5-month-old male Wistar albino rats were subjected to three times/week moderate intensity exercise on a rodent treadmill for a period of 6 weeks. The tissue antioxidant activity towards various reactive oxygen species (ROS) was determined in the hippocampus...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28711502/a-small-molecule-activator-of-sirt3-promotes-deacetylation-and-activation-of-manganese-superoxide-dismutase
#3
Jiaqi Lu, Hua Zhang, Xian Chen, Yong Zou, Jiasong Li, Li Wang, Minhao Wu, Jianye Zang, Yang Yu, Wei Zhuang, Qing Xia, Jiangyun Wang
The modulation of protein acetylation network is a promising strategy for life span extension and disease treatment.(1-2) A variety of small molecules have been developed to target deacetylases, but extremely few of these molecules are capable of activating the mitochondrial NAD-dependent deacetylase sirtuin-3 (SIRT3).(3-4) Manganese superoxide dismutase (MnSOD) is the major superoxide scavenger in mitochondria, whose activity is regulated by SIRT3-mediated deacetylation, particularly at the Lys68 site.(5) To investigate the influence of Lys68 acetylation on MnSOD activity, we produced a mutant MnSOD protein-bearing N-acetyllysine (AcK) at its Lys68 position through the genetic code expansion approach...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28707980/extranuclear-sirtuins-and-metabolic-stress
#4
Mahmoud Sobhy Elkhwanky, Jukka Hakkola
SIGNIFICANCE: Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4 and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications and ADP-ribosylation...
July 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28704962/sirt3-oncogene-and-tumor-suppressor-in-cancer
#5
REVIEW
Margalida Torrens-Mas, Jordi Oliver, Pilar Roca, Jorge Sastre-Serra
Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function...
July 12, 2017: Cancers
https://www.readbyqxmd.com/read/28699360/mir-34a-and-mir-9-are-overexpressed-and-sirt-genes-are-downregulated-in-peripheral-blood-mononuclear-cells-of-aging-humans
#6
Magdalena Owczarz, Monika Budzinska, Anna Domaszewska-Szostek, Joanna Borkowska, Jacek Polosak, Magdalena Gewartowska, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
Increased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n = 57, mean age 27 ± 4...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28698153/curcumin-prevents-cisplatin-induced-renal-alterations-in-mitochondrial-bioenergetics-and-dynamic
#7
Bibiana Ortega-Domínguez, Omar Emiliano Aparicio-Trejo, Fernando E García-Arroyo, Juan Carlos León-Contreras, Edilia Tapia, Eduardo Molina-Jijón, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, Diana Barrera-Oviedo, José Pedraza-Chaverri
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model...
July 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28687409/ephb2-signaling-mediated-sirt3-expression-reduces-msc-senescence-by-maintaining-mitochondrial-ros-homeostasis
#8
Young Hyun Jung, Hyun Jik Lee, Jun Sung Kim, Sei-Jung Lee, Ho Jae Han
Disruption of mitochondrial reactive oxygen species (mtROS) homeostasis is a key factor inducing UCB-MSC senescence. Accordingly, preventing mtROS accumulation will help in suppressing the UCB-MSC senescence. In this study, we observed that the expressions of EphrinB2 and EphB2 were inversely regulated by UCB-MSC passage-dependent manner. EphB2 signaling induced mitochondrial translocation of Sirt3. The knockdown of SIRT3 inhibited the effect of EphB2 signaling in UCB-MSCs. Subsequently, EphrinB2-Fc induced the nuclear translocation of Nrf-2 via c-Src phosphorylation dependent manner, and Sirt3 expression was regulated by Nrf-2...
July 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28684630/sirt3-impairment-and-sod2-hyperacetylation-in-vascular-oxidative-stress-and-hypertension
#9
Anna E Dikalova, Hana A Itani, Rafal R Nazarewicz, William G McMaster, Charles R Flynn, Roman V Uzhachenko, Joshua P Fessel, Jorge L Gamboa, David G Harrison, Sergey I Dikalov
Rationale: Clinical studies have shown that Sirt3 expression declines by 40% by age 65 paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 due to increased NADH and acetyl-CoA levels. Sirt3 impairment reduces the activity of a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2), due to hyperacetylation. Objective: In this study we examined if loss of Sirt3 activity increases vascular oxidative stress due to SOD2 hyperacetylation and promotes endothelial dysfunction and hypertension...
July 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28680578/dysfunctional-bmpr2-signaling-drives-an-abnormal-endothelial-requirement-for-glutamine-in-pulmonary-arterial-hypertension
#10
Robert A Egnatchik, Evan L Brittain, Amy T Shah, Wassim H Fares, H James Ford, Ken Monahan, Christie J Kang, Emily G Kocurek, Shijun Zhu, Thong Luong, Thuy T Nguyen, Erik Hysinger, Eric D Austin, Melissa C Skala, Jamey D Young, L Jackson Roberts, Anna R Hemnes, James West, Joshua P Fessel
Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28673962/potential-mechanisms-linking-sirt-activity-and-hypoxic-2-hydroxyglutarate-generation-no-role-for-direct-enzyme-de-acetylation
#11
Sergiy M Nadtochiy, Yves T Wang, Jimmy Zhang, Keith Nehrke, Xenia Schafer, Kevin Welle, Sina Ghaemmaghami, Joshua Munger, Paul S Brookes
2-hydroxyglutarate (2-HG) is a hypoxic metabolite with potentially important epigenetic signaling roles. The mechanisms underlying 2-HG generation are poorly understood, but evidence suggests a potential regulatory role for the sirtuin family of lysine deacetylases. Thus, we hypothesized that the acetylation status of the major 2-HG-generating enzymes (lactate dehydrogenase (LDH), isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH)) may govern their 2-HG generating activity. In-vitro acetylation of these enzymes, with confirmation by western blotting, mass spectrometry, reversibility by recombinant sirtuins, and an assay for global lysine occupancy, yielded no effect on 2-HG generating activity...
July 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28673739/sirtuin-3-rescues-neurons-through-the-stabilisation-of-mitochondrial-biogenetics-in-the-virally-expressing-mutant-%C3%AE-synuclein-rat-model-of-parkinsonism
#12
Jacqueline A Gleave, Lindsay R Arathoon, Dennison Trinh, Kristin E Lizal, Nicolas Giguère, James H M Barber, Zainab Najarali, M Hassan Khan, Sherri L Thiele, Mahin S Semmen, James B Koprich, Jonathan M Brotchie, James H Eubanks, Louis-Eric Trudeau, Joanne E Nash
Parkinson's disease (PD) is a neurodegenerative movement disorder, which affects approximately 1-2% of the population over 60years of age. Current treatments for PD are symptomatic, and the pathology of the disease continues to progresses over time until palliative care is required. Mitochondria are key players in the pathology of PD. Genetic and post mortem studies have shown a large number of mitochondrial abnormalities in the substantia nigra pars compacta (SNc) of the parkinsonian brain. Furthermore, physiologically, mitochondria of nigral neurons are constantly under unusually high levels of metabolic stress because of the excitatory properties and architecture of these neurons...
July 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28670394/pfp-alleviates-nonalcoholic-steatohepatitis-fatty-liver-in-both-apo-e-mice-and-changliver-cell-s
#13
Dong Yan, Yuan-Yuan Wei, Xiu-Mei Li, Xiu-Chao Sun, Zhong Wang, Haji Akber Aisa
High-calorie food leads to nonalcoholic fatty liver disease (NAFLD) through the dysregulation of genes involved in lipid metabolism, but the precise mechanism is still unknown. Pomegranate flowers are used to treat diabetes mellitus in traditional Uighur medicine. Here we sought to investigate the effect and mechanism of pomegranate flower polyphenols (PFP) on NAFLD Apo E(-/-) mice induced by a high-fat diet (HFD) and whether PFP improves NAFLD through decreasing oxidative stress. PFP supplementation in mice significantly reduced the HFD-induced gains in body weight compared with the mice fed only with HFD...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28662362/sirt3-dependent-deacetylation-of-sod2-plays-a-protective-role-against-oxidative-stress-in-oocytes-from-diabetic-mice
#14
Xiaohui Liu, Liang Zhang, Pan Wang, Xiaoyan Li, Danhong Qiu, Ling Li, Jiaqi Zhang, Xiaojing Hou, Longsen Han, Juan Ge, Mo Li, Ling Gu, Qiang Wang
Maternal diabetes has been demonstrated to adversely affect oocyte quality in mouse oocytes. However, the potential molecular mechanisms are poorly understood. Here, we established a type I diabetic mouse model and detected the increased reactive oxygen species (ROS) levels and decreased Sirt3 expression in oocytes from diabetic mice. Furthermore, we found that forced expression of Sirt3 in diabetic oocytes significantly attenuates such an excessive production of ROS. The acetylation status of lysine 68 of superoxide dismutase (SOD2K68) is dependent on Sirt3 in oocytes...
June 29, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28659809/corrigendum-high-sensitivity-of-sirt3-deficient-hearts-to-ischemia-reperfusion-is-associated-with-mitochondrial-abnormalities
#15
Rebecca M Parodi-Rullán, Xavier Chapa-Dubocq, Pedro J Rullán, Sehwan Jang, Sabzali Javadov
[This corrects the article on p. 275 in vol. 8, PMID: 28559847.].
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28658527/melatonin-protects-against-maternal-obesity-associated-oxidative-stress-and-meiotic-defects-in-oocytes-via-the-sirt3-sod2-dependent-pathway
#16
Longsen Han, Haichao Wang, Ling Li, Xiaoyan Li, Juan Ge, Russel J Reiter, Qiang Wang
Maternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high-fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice...
June 28, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#17
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28638677/changes-in-sirtuin-2-and-sirtuin-3-mrna-expressions-in-rheumatoid-arthritis
#18
Murat Kara, Servet Yolbaş, Cem Şahin, Süleyman Serdar Koca
OBJECTIVE: Sirtuins (SIRTs) play a prominent role in metabolism, apoptosis, aging, inflammation, and epigenetics. Inflammation, apoptosis, and epigenetics are pathogenic issues in rheumatoid arthritis (RA). This study aimed to evaluate SIRT2 and SIRT3 mRNA expressions in patients with RA. MATERIAL AND METHODS: Fifty-four patients with RA and 26 healthy controls were enrolled. Disease activity was determined using the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (score of >2...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28634345/sirtuin-3-deficiency-does-not-alter-host-defenses-against-bacterial-and-fungal-infections
#19
Eleonora Ciarlo, Tytti Heinonen, Jérôme Lugrin, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. SIRT3 deficiency has been reported to promote chronic inflammation-related disorders, but whether SIRT3 impacts on innate immune responses and host defenses against infections remains essentially unknown. This aspect is of primary importance considering the great interest in developing SIRT3-targeted therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620018/correction-for-papa-and-germain-sirt3-regulates-a-novel-arm-of-the-mitochondrial-unfolded-protein-response
#20
Luena Papa, Doris Germain
No abstract text is available yet for this article.
July 1, 2017: Molecular and Cellular Biology
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