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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
Francesco Bellomo, Anna Signorile, Grazia Tamma, Marianna Ranieri, Francesco Emma, Domenico De Rasmo
Nephropathic cystinosis (NC) is a rare disease caused by mutations in the CTNS gene encoding for cystinosin, a lysosomal transmembrane cystine/H+ symporter, which promotes the efflux of cystine from lysosomes to cytosol. NC is the most frequent cause of Fanconi syndrome (FS) in young children, the molecular basis of which is not well established. Proximal tubular cells have very high metabolic rate due to the active transport of many solutes. Not surprisingly, mitochondrial disorders are often characterized by FS...
March 16, 2018: Cellular and Molecular Life Sciences: CMLS
Wen-Jun Yan, Ruo-Bin Liu, Ling-Kai Wang, Ya-Bing Ma, Shao-Li Ding, Fei Deng, Zhong-Yuan Hu, Da-Bin Wang
Endoplasmic reticulum (ER) stress occurring in stringent conditions is critically involved in neuronal survival and death. Resveratrol is a non-flavonoid polyphenol that has neuroprotective effects against many neurological disorders. Here, we investigated the potential protective effects of resveratrol in an in vitro ER stress model mimicked by tunicamycin (TM) treatment in neuronal HT22 cells. We found that TM dose-dependently decreased cell viability and increased apoptosis, which were both significantly attenuated by resveratrol treatment...
2018: Frontiers in Neuroscience
Yan Li, Ying Ma, Liqiang Song, Lu Yu, Le Zhang, Yingmei Zhang, Yuan Xing, Yue Yin, Heng Ma
Mitochondrial dynamics have critical roles in aging, and their impairment represents a prominent risk factor for myocardial dysfunction. Mitochondrial deacetylase sirtuin (SIRT)3 contributes greatly to the prevention of redox stress and cell aging. The present study explored the role of SIRT3 on myocardium aging. Western blot analysis demonstrated that SIRT3 expression levels were significantly lower in the myocardia of aged mice compared with young mice. Immunoprecipitation and western blot assays indicated that the activity of mitochondrial manganese superoxide dismutase (MnSOD) and peroxisome proliferator‑activated receptor γ coactivator (PGC)‑1α was reduced in the aged heart...
March 9, 2018: International Journal of Molecular Medicine
Francesca Martorana, Daniela Gaglio, Maria Rosaria Bianco, Federica Aprea, Assunta Virtuoso, Marcella Bonanomi, Lilia Alberghina, Michele Papa, Anna Maria Colangelo
Neuronal differentiation involves extensive modification of biochemical and morphological properties to meet novel functional requirements. Reorganization of the mitochondrial network to match the higher energy demand plays a pivotal role in this process. Mechanisms of neuronal differentiation in response to nerve growth factor (NGF) have been largely characterized in terms of signaling, however, little is known about its impact on mitochondrial remodeling and metabolic function. In this work, we show that NGF-induced differentiation requires the activation of autophagy mediated by Atg9b and Ambra1, as it is disrupted by their genetic knockdown and by autophagy blockers...
March 9, 2018: Cell Death & Disease
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
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...
March 1, 2018: Molecular Medicine Reports
Hsien-Chun Chiu, Chen-Yuan Chiu, Rong-Sen Yang, Ding-Cheng Chan, Shing-Hwa Liu, Chih-Kang Chiang
BACKGROUND: A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women...
March 6, 2018: Journal of Cachexia, Sarcopenia and Muscle
R Wang, J-Y Zhang, M Zhang, M-G Zhai, S-Y Di, Q-H Han, Y-P Jia, M Sun, H-L Liang
OBJECTIVE: Ischemia-reperfusion (IR) injury remains an unresolved and complicated situation in clinical practice. In this study, H9c2 cardiomyocytes were subjected to curcumin (Cur) treatment in the absence or presence of the silent information regulator 3 (SIRT3) inhibitor 3-TYP and were then subjected to IR. MATERIALS AND METHODS: H9c2 cells and male Sprague-Dawley (SD) rats were cultured. MTT assay was performed to assess H9c2 cell viability. Cellular apoptosis was analyzed by TUNEL assay...
February 2018: European Review for Medical and Pharmacological Sciences
Yi-Xuan Guo, Hai-Tao Nie, Chen-Jie Xu, Guo-Min Zhang, Ling-Wei Sun, Ting-Ting Zhang, Zhen Wang, Xu Feng, Pei-Hua You, Feng Wang
The aim of this study was to determine whether nutrient restriction and arginine treatment affect energy metabolism changes and oxidative stress through the mitochondrial pathway in the ovarian tissue of ewes during the luteal phase. On days 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9), and l-arginine group (AG; n = 9) administered Arg treatment (or vehicle) three times per day...
February 22, 2018: Theriogenology
Karina N Gonzalez Herrera, Elma Zaganjor, Yoshinori Ishikawa, Jessica B Spinelli, Haejin Yoon, Jia-Ren Lin, F Kyle Satterstrom, Alison Ringel, Stacy Mulei, Amanda Souza, Joshua M Gorham, Craig C Benson, Jonathan G Seidman, Peter K Sorger, Clary B Clish, Marcia C Haigis
Sirtuin 3 (SIRT3) is a NAD+ -dependent deacetylase downregulated in aging and age-associated diseases such as cancer and neurodegeneration and in high-fat diet (HFD)-induced metabolic disorders. Here, we performed a small-molecule screen and identified an unexpected metabolic vulnerability associated with SIRT3 loss. Azaserine, a glutamine analog, was the top compound that inhibited growth and proliferation of cells lacking SIRT3. Using stable isotope tracing of glutamine, we observed its increased incorporation into de novo nucleotide synthesis in SIRT3 knockout (KO) cells...
February 20, 2018: Cell Reports
Carla Tatone, Giovanna Di Emidio, Arcangelo Barbonetti, Gaspare Carta, Alberto M Luciano, Stefano Falone, Fernanda Amicarelli
BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking...
February 13, 2018: Human Reproduction Update
Dan Li, Qianyu Liu, Wen Sun, Xiuping Chen, Ying Wang, Yuxiang Sun, Ligen Lin
BACKGROUND AND PURPOSE: Chronic inflammation in adipose tissue is critical in the onset and development of insulin resistance and type 2 diabetes. Macrophage infiltration into adipose tissue and pro-inflammatory polarization play key roles in adipose tissue inflammation. The fruit hull of mangosteen (Garcinia mangostana) has been used in traditional medicine for treatment of various inflammatory diseases. However, its role in regulating adipose tissue inflammation is unexplored. This study was designed to identify xanthones from G...
February 15, 2018: British Journal of Pharmacology
Juan-Juan Li, Shun-Jin Liu, Xiao-Yu Liu, Eng-Ang Ling
BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-1bea (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia...
February 14, 2018: Current Medicinal Chemistry
Daniel S Gaul, Julien Weber, Lambertus J Van Tits, Susanna Sluka, Lisa Pasterk, Martin F Reiner, Natacha Calatayud, Christine Lohmann, Roland Klingenberg, Jürgen Pahla, Daria Vdovenko, Felix C Tanner, Giovanni G Camici, Urs Eriksson, Johan Auwerx, François Mach, Stephan Windecker, Nicolas Rodondi, Thomas F L Uuml Scher, Stephan Winnik, Christian M Matter
BACKGROUND: Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3-/- mice (n = 6) was reduced by half compared to Sirt3+/+ wildtype (WT, n = 8, p<0...
February 10, 2018: Cardiovascular Research
Samar Sultan, Nada Alzahrani, Kalthoom Al-Sakkaf
Gestational diabetes mellitus (GDM) is a glucose intolerance disorder which occurs during pregnancy as a result of insulin insensitivity; it usually disappears after delivery. However, some women with GDM can develop type 2 diabetes (T2D) after delivery, and the mechanisms by which this occurs remain unknown. This study compared the levels of sirtuins (NAD-dependent deacetylases) and antioxidative enzymes in postpartum women with previous GDM (pGDM) or T2D and in postpartum women with a previous healthy pregnancy (controls)...
February 2018: FEBS Open Bio
Yujun Hou, Sofie Lautrup, Stephanie Cordonnier, Yue Wang, Deborah L Croteau, Eduardo Zavala, Yongqing Zhang, Kanako Moritoh, Jennifer F O'Connell, Beverly A Baptiste, Tinna V Stevnsner, Mark P Mattson, Vilhelm A Bohr
Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ+/- mice have a reduced cerebral NAD+ /NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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
Rong Li, Yizhou Quan, Weiliang Xia
SIRT3, a mitochondrial NAD+-dependent deacetylase, has been reported to restrain prostate cancer growth both in vitro and in vivo, however, its role in metastatic prostate cancer has not been revealed. In this study, we reported that SIRT3 inhibited the epithelial-mesenchymal transition (EMT) and migration of prostatic cancer cells in vitro and their metastasis in vivo. Consistently, based on analyses of tissue microarray and microarray datasets, lower SIRT3 expression level was correlated with higher prostate cancer Gleason scores, and SIRT3 expression were significantly decreased in metastatic tissues compared with prostate tumor tissues...
February 5, 2018: Experimental Cell Research
Neha Mishra, Sonam Lata, Priyanka Deshmukh, Kajal Kamat, Avadhesha Surolia, Tanushree Banerjee
Cellular stress like ER and oxidative stress are the principle causative agents of various proteinopathies. Multifunctional protein PARK7/DJ-1 provides protection against cellular stress. Recently, insulin/IGF also has emerged as a neuro-protective molecule. However, it is not known whether DJ-1 and insulin/IGF complement each other for cellular protection in response to stress. In this study, we show for the first time, that in human and mouse neuronal cell lines, down regulation of DJ-1 for 48 h leads to compensatory upregulation of insulin/IGF signaling (IIS) pathway genes, namely, insulin receptor, insulin receptor substrate, and Akt under normal physiological conditions as well as in cellular stress conditions...
February 7, 2018: BioFactors
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