keyword
MENU ▼
Read by QxMD icon Read
search

SIRT5

keyword
https://www.readbyqxmd.com/read/29769314/ablation-of-sirtuin5-in-the-postnatal-mouse-heart-results-in-protein-succinylation-and-normal-survival-in-response-to-chronic-pressure-overload
#1
Kathleen A Hershberger, Dennis M Abraham, Juan Liu, Jason W Locasale, Paul A Grimsrud, Matthew D Hirschey
Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function and metabolism under stress. Previously, we described a phenotype of increased mortality in whole-body SIRT5KO mice exposed to chronic pressure overload compared to their littermate WT controls. To determine if the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5, we developed a tamoxifen-inducible, heart-specific SIRT5KO mouse model...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29622432/sirtuin-5-as-a-novel-target-to-blunt-blood-brain-barrier-damage-induced-by-cerebral-ischemia-reperfusion-injury
#2
Candela Diaz-Cañestro, Mario Merlini, Nicole R Bonetti, Luca Liberale, Patricia Wüst, Sylvie Briand-Schumacher, Jan Klohs, Sara Costantino, Melroy Miranda, Gabriele Schoedon-Geiser, Gerd A Kullak-Ublick, Alexander Akhmedov, Francesco Paneni, Jürg H Beer, Thomas F Lüscher, Giovanni G Camici
BACKGROUND: In acute ischemic stroke (AIS) patients, impaired blood-brain barrier (BBB) integrity is associated with hemorrhagic transformation and worsened outcome. Yet, the mechanisms underlying these relationships are poorly understood and consequently therapeutic strategies are lacking. This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury. METHODS AND RESULTS: SIRT5 knockout (SIRT5-/- ) and wild type (WT) mice underwent transient middle cerebral artery (MCA) occlusion (tMCAO) followed by 48h of reperfusion...
June 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29565454/sirt5-as-a-biomarker-for-response-to-anthracycline-taxane-based-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#3
Lu Xu, Xiaofang Che, Ying Wu, Na Song, Sha Shi, Shuo Wang, Ce Li, Lingyun Zhang, Xinlian Zhang, Xiujuan Qu, Yuee Teng
Neoadjuvant chemotherapy (NAC) is of great importance for patients with triple-negative breast cancer (TNBC) and the achievement of pathological complete response (pCR) to NAC in TNBC patients indicates survival benefits. However, the identification of reliable predictive biomarkers of pCR to NAC in TNBC patients remains an urgent and largely unattended medical issue. In the present study, we evaluated the differentially expressed genes (DEGs) between pCR and non-pCR patients after doxorubicin/cyclophosphamide therapy, followed by paclitaxel pre-operative treatment in 64 TNBC patients recorded in the GSE41998 dataset of Gene Expression Omnibus and identified 118 DEGs...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29557214/current-understanding-and-future-perspectives-of-the-roles-of-sirtuins-in-the-reprogramming-and-differentiation-of-pluripotent-stem-cells
#4
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29514096/targeting-a-sirt5-positive-subpopulation-overcomes-multidrug-resistance-in-wild-type-kras-colorectal-carcinomas
#5
ZunGuo Du, XiuJuan Liu, Tao Chen, WenChao Gao, ZhengMing Wu, ZhiQian Hu, Dong Wei, ChunFang Gao, QingQuan Li
A major obstacle for successful management of patients with colorectal carcinoma (CRC) is resistance to anti-cancer cytotoxic treatments. Here, we identified a mechanism of multidrug resistance in wild-type Kras CRCs based on the survival of a cell subpopulation characterized by Sirt5 expression. Sirt5+ cells in wild-type Kras CRCs are resistant to either chemotherapeutic agents or cetuximab and serve as a reservoir for recurrence. Sirt5 demalonylates and inactivates succinate dehydrogenase complex subunit A (SDHA), leading to an accumulation of the oncometabolite succinate...
March 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29514063/the-mitochondrial-acylome-emerges-proteomics-regulation-by-sirtuins-and-metabolic-and-disease-implications
#6
REVIEW
Chris Carrico, Jesse G Meyer, Wenjuan He, Brad W Gibson, Eric Verdin
Post-translational modification of lysine residues via reversible acylation occurs on proteins from diverse pathways, functions, and organisms. While nuclear protein acylation reflects the competing activities of enzymatic acyltransferases and deacylases, mitochondrial acylation appears to be driven mostly via a non-enzymatic mechanism. Three protein deacylases, SIRT3, SIRT4, and SIRT5, reside in the mitochondria and remove these modifications from targeted proteins in an NAD+ -dependent manner. Recent proteomic surveys of mitochondrial protein acylation have identified the sites of protein acetylation, succinylation, glutarylation, and malonylation and their regulation by SIRT3 and SIRT5...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29512733/autophagy-inhibition-enhanced-5%C3%A2-fu%C3%A2-induced-cell-death-in-human-gastric-carcinoma-bgc%C3%A2-823-cells
#7
Xing-Xing He, Chen-Kai Huang, Bu-Shan Xie
The exact molecular mechanism of 5-fluorouracil (5-FU) in human gastric cancer cells remains to be elucidated. Cultured BGC‑823 human gastric carcinoma and AGS cell lines were treated with 5‑FU. Autophagosome formation was investigated through multiple approaches, including the quantification of green fluorescent protein‑microtubule‑associated protein 1A/1B‑light chain 3 (LC3) puncta, LC3 conversion and electron microscopy observations. Additionally, autophagy was inhibited using 3‑methyladenine (3‑MA) and beclin‑1 ablation, to determine its role in 5‑FU‑mediated cell death...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29494161/potent-and-selective-inhibitors-of-human-sirtuin-5
#8
Diana Kalbas, Sandra Liebscher, Theresa Nowak, Marat Meleshin, Martin Pannek, Corinna Popp, Zayan Alhalabi, Frank Bordusa, Wolfgang Sippl, Clemens Steegborn, Mike Schutkowski
Sirtuins are protein deacylases that regulate metabolism and stress responses and are implicated in aging-related diseases. Modulators of the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, e.g., for cancer. Selective and potent inhibitors are available for Sirt2, but selective inhibitors for Sirt5 with Ki values in the low nanomolar range are lacking. We synthesized and screened 3-arylthiosuccinylated and 3-benzylthiosuccinylated peptide derivatives yielding Sirt5 inhibitors with low-nanomolar Ki values...
March 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29491006/sirt5-inhibits-peroxisomal-acox1-to-prevent-oxidative-damage-and-is-downregulated-in-liver-cancer
#9
Xiu-Fei Chen, Meng-Xin Tian, Ren-Qiang Sun, Meng-Li Zhang, Li-Sha Zhou, Lei Jin, Lei-Lei Chen, Wen-Jie Zhou, Kun-Long Duan, Yu-Jia Chen, Chao Gao, Zhou-Li Cheng, Fang Wang, Jin-Ye Zhang, Yi-Ping Sun, Hong-Xiu Yu, Yu-Zheng Zhao, Yi Yang, Wei-Ren Liu, Ying-Hong Shi, Yue Xiong, Kun-Liang Guan, Dan Ye
Peroxisomes account for ~35% of total H2 O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl-CoA oxidase 1) is the first and rate-limiting enzyme in fatty acid β-oxidation and a major producer of H2 O2 ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5-mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers...
May 2018: EMBO Reports
https://www.readbyqxmd.com/read/29463709/identification-of-the-yeats-domain-of-gas41-as-a-ph-dependent-reader-of-histone-succinylation
#10
Yi Wang, Jing Jin, Matthew Wai Heng Chung, Ling Feng, Hongyan Sun, Quan Hao
Lysine succinylation is a newly discovered posttranslational modification with distinctive physical properties. However, to date rarely have studies reported effectors capable of interpreting this modification on histones. Following our previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we identified the GAS41 YEATS domain as a reader of Ksuc on histones. Biochemical studies showed that the GAS41 YEATS domain presents significant binding affinity toward H3K122suc upon a protonated histidine residue...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29440987/metabolomics-based-identification-of-sirt5-and-protein-kinase-c-epsilon-regulated-pathways-in-brain
#11
Kevin B Koronowski, Nathalie Khoury, Kahlilia C Morris-Blanco, Holly M Stradecki-Cohan, Timothy J Garrett, Miguel A Perez-Pinzon
The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5-/- mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance. The aim of this study was to identify the SIRT5-regulated metabolic pathways in the brain and determine which of those pathways are linked to PKCε. Our results show SIRT5 is primarily expressed in neurons and endothelial cells in the brain, with mitochondrial and extra-mitochondrial localization...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29422688/lc-ms-ms-based-quantitative-study-of-the-acyl-group-and-site-selectivity-of-human-sirtuins-to-acylated-nucleosomes
#12
Kana Tanabe, Jiaan Liu, Daiki Kato, Hitoshi Kurumizaka, Kenzo Yamatsugu, Motomu Kanai, Shigehiro A Kawashima
Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29416026/sirtuin5-contributes-to-colorectal-carcinogenesis-by-enhancing-glutaminolysis-in-a-deglutarylation-dependent-manner
#13
Yun-Qian Wang, Hao-Lian Wang, Jie Xu, Juan Tan, Lin-Na Fu, Ji-Lin Wang, Tian-Hui Zou, Dan-Feng Sun, Qin-Yan Gao, Ying-Xuan Chen, Jing-Yuan Fang
Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13 C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29408602/hepatic-nad-levels-and-nampt-abundance-are-unaffected-during-prolonged-high-fat-diet-consumption-in-c57bl-6jbomtac-mice
#14
Morten Dall, Melanie Penke, Karolina Sulek, Madlen Matz-Soja, Birgitte Holst, Antje Garten, Wieland Kiess, Jonas T Treebak
Dietary supplementation of nicotinamide adenine dinucleotide (NAD+ ) precursors has been suggested as a treatment for non-alcoholic fatty liver disease and obesity. In the liver, NAD+ is primarily generated by nicotinamide phosphoribosyltransferase (NAMPT), and hepatic levels of NAMPT and NAD+ have been reported to be dependent on age and body composition. The aim of the present study was to identify time course-dependent changes in hepatic NAD content and NAD+ salvage capacity in mice challenged with a high-fat diet (HFD)...
February 2, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29300832/analysis-of-polymorphisms-in-58-potential-candidate-genes-for-association-with-human-longevity
#15
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Maarit Tiirikainen, Bradley J Willcox
Longevity is a polygenic trait in which genetic predisposition is particularly important. We hypothesized that amongst genes differentially expressed in response to caloric restriction, several may be candidate longevity genes. We tested 459 single nucleotide polymorphisms (SNPs) in 46 genes differentially expressed in calorically-restricted mice and 12 other genes for association with longevity. Subjects were American men of Japanese ancestry, 440 aged ≥95 years and 374 with an average lifespan. Based on a dominant model of inheritance, an association with longevity at the p < 0...
December 30, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29261224/mitochondrial-sirtuins-in-the-rat-adrenal-gland-location-within-the-glands-of-males-and-females-hormonal-and-developmental-regulation-of-gene-expressions
#16
Piotr Celichowski, Karol Jopek, Marta Szyszka, Marianna Tyczewska, Ludwik K Malendowicz, Marcin Rucinski
INTRODUCTION: Sirtuins are NAD dependent class III histone deacetylases. In adrenal cortex mitochondria are able to transform - via nicotinamide nucleotide transhydrogenase (NNT) - NAD into NADPH, which is required for steroidogenesis. These findings suggest that sirtuins expressed in mitochondria, Sirt3, Sirt4 and Sirt5, may be associated with adrenal steroidogenesis. Therefore, the purpose of this study was to characterize the expression of mitochondrial sirtuins (Sirt3-5) in individual compartments of rat adrenal cortex, their developmental regulation and to demonstrate whether their expression is dependent on adrenocorticotrophic hormone (ACTH) and Nampt (nicotinamide phosphoribosyltransferase also known as visfatin/PBEF), the rate-limiting enzyme in the regulation of mammalian NAD synthesis...
2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29249955/expression-of-sirtuins-in-the-retinal-neurons-of-mice-rats-and-humans
#17
Hongdou Luo, Min Zhou, Kaibao Ji, Jiejie Zhuang, Wenjie Dang, Shiya Fu, Tao Sun, Xu Zhang
Sirtuins are a class of histone deacetylases (HDACs) that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7) that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29180469/shmt2-desuccinylation-by-sirt5-drives-cancer-cell-proliferation
#18
Xin Yang, Zhe Wang, Xin Li, Boya Liu, Minghui Liu, Lu Liu, Shuaiyi Chen, Mengmeng Ren, Yankun Wang, Miao Yu, Bo Wang, Junhua Zou, Wei-Guo Zhu, Yuxin Yin, Wei Gu, Jianyuan Luo
The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in serine catabolism, drives cancer cell proliferation, but how this role is regulated is undefined. Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine catabolism in tumor cells. SIRT5 interaction directly mediated desuccinylation of lysine 280 on SHMT2, which was crucial for activating its enzymatic activity. Conversely, hypersuccinylation of SHMT2 at lysine 280 was sufficient to inhibit its enzymatic activity and downregulate tumor cell growth in vitro and in vivo Notably, SIRT5 inactivation led to SHMT2 enzymatic downregulation and to abrogated cell growth under metabolic stress...
January 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29154835/sirt5-and-post-translational-protein-modifications-a-potential-therapeutic-target-for-myocardial-ischemia-reperfusion-injury-with-regard-to-mitochondrial-dynamics-and-oxidative-metabolism
#19
REVIEW
Rongjun Zou, Wanting Shi, Jun Tao, Hongmu Li, Xifeng Lin, Songran Yang, Ping Hua
SIRT5 is a sirtuin family member that participates in dynamic and reversible protein chemical modification after translation. It has pivotal roles in the regulation of numerous aspects of myocardial energy metabolism and cardiac functions. Recent studies suggest that down-regulation of this regulator significantly increased the extent of myocardial infarction during ischemia-reperfusion injury (IRI). Accordingly, SIRT5 is emerging as a major contributor to the pathogenesis of IRI and may possess therapeutic potential for reversing mitochondrial respiratory chain disturbances and cellular damage attributed to ischemia-reperfusion...
January 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29138502/crystal-structures-of-the-mitochondrial-deacylase-sirtuin-4-reveal-isoform-specific-acyl-recognition-and-regulation-features
#20
Martin Pannek, Zeljko Simic, Matthew Fuszard, Marat Meleshin, Dante Rotili, Antonello Mai, Mike Schutkowski, Clemens Steegborn
Sirtuins are evolutionary conserved NAD+ -dependent protein lysine deacylases. The seven human isoforms, Sirt1-7, regulate metabolism and stress responses and are considered therapeutic targets for aging-related diseases. Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis. In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4. Here we describe acyl substrates and crystal structures for Sirt4...
November 15, 2017: Nature Communications
keyword
keyword
29429
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"