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https://www.readbyqxmd.com/read/29847346/hereditary-ataxias-and-paraparesias-clinical-and-genetic-update
#1
Livia Parodi, Giulia Coarelli, Giovanni Stevanin, Alexis Brice, Alexandra Durr
PURPOSE OF REVIEW: This review aims at updating the clinical and genetic aspects of hereditary spastic paraplegias (HSPs) and hereditary cerebellar ataxias (HCAs), focusing on the concept of spastic-ataxia phenotypic spectrum and on newly identified clinical overlaps with other neurological and nonneurological diseases. RECENT FINDINGS: Next-generation sequencing (NGS) has allowed the discovery of new genes involved in HSPs and HCAs. They include new HCAs genes such as GRM1 (SCA44), FAT2 (SCA45), PLD3 (SCA46), SCYL1 (SCAR21), UBA5 (SCAR24) and XRCC1 (SCAR26) as well as CAPN1 (SPG76) and CPT1C (SPG73) in HSPs...
May 29, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29730527/evolutionary-analysis-of-the-carnitine-and-choline-acyltransferases-suggests-distinct-evolution-of-cpt2-versus-cpt1-and-related-variants
#2
Marjanne D van der Hoek, Ole Madsen, Jaap Keijer, Feike R van der Leij
Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensive phylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2...
May 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29725060/cpt1c-promotes-human-mesenchymal-stem-cells-survival-under-glucose-deprivation-through-the-modulation-of-autophagy
#3
Xavier Roa-Mansergas, Rut Fadó, Maher Atari, Joan F Mir, Helena Muley, Dolors Serra, Núria Casals
Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29720080/genome-wide-scan-reveals-population-stratification-and-footprints-of-recent-selection-in-nelore-cattle
#4
Diercles F Cardoso, Lucia Galvão de Albuquerque, Christian Reimer, Saber Qanbari, Malena Erbe, André V do Nascimento, Guilherme C Venturini, Daiane C Becker Scalez, Fernando Baldi, Gregório M Ferreira de Camargo, Maria E Zerlotti Mercadante, Joslaine N do Santos Gonçalves Cyrillo, Henner Simianer, Humberto Tonhati
BACKGROUND: This study aimed at (1) assessing the genomic stratification of experimental lines of Nelore cattle that have experienced different selection regimes for growth traits, and (2) identifying genomic regions that have undergone recent selection. We used a sample of 763 animals genotyped with the Illumina BovineHD BeadChip, among which 674 animals originated from two lines that are maintained under directional selection for increased yearling body weight and 89 animals from a control line that is maintained under stabilizing selection...
May 2, 2018: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/29568887/genome-wide-analysis-of-dna-methylation-in-human-peripheral-leukocytes-identifies-potential-biomarkers-of-nonalcoholic-fatty-liver-disease
#5
Rui-Nan Zhang, Qin Pan, Rui-Dan Zheng, Yu-Qiang Mi, Feng Shen, Da Zhou, Guang-Yu Chen, Chan-Yan Zhu, Jian-Gao Fan
The aim of the present study was to uncover the role of leukocytic DNA methylation in the evaluation of nonalcoholic fatty liver disease (NAFLD). Patients with biopsy-proven NAFLD (n=35) and normal controls (n=30) were recruited from Chinese Han population. Their DNA methylation in peripheral leukocytes was subjected to genome-wide profiling. The association between differential methylation of CpG sites and NAFLD was further investigated on the basis of histopathological classification, bioinformatics, and pyrosequencing...
July 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29472517/nordihydroguaiaretic-acid-a-lignan-from-larrea-tridentata-creosote-bush-protects-against-american-lifestyle-induced-obesity-syndrome-diet-induced-metabolic-dysfunction-in-mice
#6
Jackie K W Chan, Stefanie Bittner, Alex Bittner, Suman Atwal, Wen-Jun Shen, Mohammed Inayathullah, Jayakumar Rajada, Mark R Nicolls, Fredric B Kraemer, Salman Azhar
To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content...
May 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29346768/activation-of-ampk-regulated-crh-neurons-in-the-pvh-is-sufficient-and-necessary-to-induce-dietary-preference-for-carbohydrate-over-fat
#7
Shiki Okamoto, Tatsuya Sato, Michihiro Tateyama, Haruaki Kageyama, Yuko Maejima, Masanori Nakata, Satoshi Hirako, Takashi Matsuo, Sanda Kyaw, Tetsuya Shiuchi, Chitoku Toda, Udval Sedbazar, Kumiko Saito, Nur Farehan Asgar, Boyang Zhang, Shigefumi Yokota, Kenta Kobayashi, Fabienne Foufelle, Pascal Ferré, Masamitsu Nakazato, Hiroaki Masuzaki, Seiji Shioda, Toshihiko Yada, Barbara B Kahn, Yasuhiko Minokoshi
Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29317762/carnitine-palmitoyltransferase-1c-regulates-cancer-cell-senescence-through-mitochondria-associated-metabolic-reprograming
#8
Yongtao Wang, Yixin Chen, Lihuan Guan, Huizheng Zhang, Yaoyao Huang, Caroline H Johnson, Zeming Wu, Frank J Gonzalez, Aiming Yu, Peng Huang, Ying Wang, Shouhui Yang, Pan Chen, Xiaomei Fan, Min Huang, Huichang Bi
Cellular senescence is a fundamental biological process that has profound implications in cancer development and therapeutics, but the underlying mechanisms remain elusive. Here we show that carnitine palmitoyltransferase 1C (CPT1C), an enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation, plays a major role in the regulation of cancer cell senescence through mitochondria-associated metabolic reprograming. Metabolomics analysis suggested alterations in mitochondria activity, as revealed by the marked decrease in acylcarnitines in senescent human pancreatic carcinoma PANC-1 cells, indicating low CPT1C activity...
March 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29151954/cpt1c-regulated-by-ampk-promotes-papillary-thyroid-carcinomas-cells-survival-under-metabolic-stress-conditions
#9
Rui Wang, Yajun Cheng, Dongwei Su, Boshen Gong, Xiaobo He, Xinyu Zhou, Zhijun Pang, Lingtao Cheng, Yuelei Chen, Zhenzhen Yao
Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29018241/eugenol-inhibits-oxidative-phosphorylation-and-fatty-acid-oxidation-via-downregulation-of-c-myc-pgc-1%C3%AE-err%C3%AE-signaling-pathway-in-mcf10a-ras-cells
#10
Xianxin Yan, Guijuan Zhang, Fengjie Bie, Yanhong Lv, Yi Ma, Min Ma, Yurong Wang, Xiaoqian Hao, Naijun Yuan, Xuefeng Jiang
Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a major volatile constituent of clove essential oil mainly obtained from Syzygium, has been reported as a potential chemopreventive drug. However, the mechanism by which Eu regulates cellular energy metabolism is still not well defined. This study was designed to determine the effect of Eu on cellular energy metabolism during early cancer progression employing untransformed and H-ras oncogene transfected MCF10A human breast epithelial cells...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818208/catecholamine-dependent-%C3%AE-adrenergic-signaling-in-a-pluripotent-stem-cell-model-of-takotsubo-cardiomyopathy
#11
Thomas Borchert, Daniela Hübscher, Celina I Guessoum, Tuan-Dinh D Lam, Jelena R Ghadri, Isabel N Schellinger, Malte Tiburcy, Norman Y Liaw, Yun Li, Jan Haas, Samuel Sossalla, Mia A Huber, Lukas Cyganek, Claudius Jacobshagen, Ralf Dressel, Uwe Raaz, Viacheslav O Nikolaev, Kaomei Guan, Holger Thiele, Benjamin Meder, Bernd Wollnik, Wolfram-Hubertus Zimmermann, Thomas F Lüscher, Gerd Hasenfuss, Christian Templin, Katrin Streckfuss-Bömeke
BACKGROUND: Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. OBJECTIVES: The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28675162/ampa-receptor-specific-biogenesis-complexes-control-synaptic-transmission-and-intellectual-ability
#12
Aline Brechet, Rebecca Buchert, Jochen Schwenk, Sami Boudkkazi, Gerd Zolles, Karine Siquier-Pernet, Irene Schaber, Wolfgang Bildl, Abdelkrim Saadi, Christine Bole-Feysot, Patrick Nitschke, Andre Reis, Heinrich Sticht, Nouriya Al-Sanna'a, Arndt Rolfs, Akos Kulik, Uwe Schulte, Laurence Colleaux, Rami Abou Jamra, Bernd Fakler
AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission in the brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled constituents of their proteome. Here we identify AMPAR complexes that transiently form in the endoplasmic reticulum (ER) and lack the core-subunits typical for AMPARs in the plasma membrane. Central components of these ER AMPARs are the proteome constituents FRRS1l (C9orf4) and CPT1c that specifically and cooperatively bind to the pore-forming GluA1-4 proteins of AMPARs...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28501436/identification-of-the-bovine-hsl-gene-expression-profiles-and-its-association-with-fatty-acid-composition-and-fat-deposition-traits
#13
Xibi Fang, Zhihui Zhao, Ping Jiang, Haibin Yu, Hang Xiao, Runjun Yang
Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolysing a variety of esters and is considered to be a candidate gene affecting fat deposition traits. Gene expression profiles of HSL were analysed in various adipose tissues of cattle, and the effect of HSL on lipid metabolism genes was analysed by a PCR array. Novel polymorphisms were identified within the HSL regulatory domain by sequencing, and the relationship between HSL variants and fat deposition traits was analysed. HSL mRNA was highly expressed in the subcutaneous and visceral fat of cattle...
May 6, 2017: Meat Science
https://www.readbyqxmd.com/read/28472467/hypothalamic-regulation-of-liver-and-muscle-nutrient-partitioning-by-brain-specific-carnitine-palmitoyltransferase-1c-in-male-mice
#14
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase (CPT) 1C, a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning and in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) during both fasting and DIO...
July 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28334197/ppar%C3%AE-regulates-tumor-cell-proliferation-and-senescence-via-a-novel-target-gene-carnitine-palmitoyltransferase-1c
#15
Yixin Chen, Yongtao Wang, Yaoyao Huang, Hang Zeng, Bingfang Hu, Lihuan Guan, Huizhen Zhang, Ai-Ming Yu, Caroline H Johnson, Frank J Gonzalez, Min Huang, Huichang Bi
Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor α (PPARα) is a ligand-activated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARα regulates CPT1C and then affects cancer cell proliferation and senescence...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/27864612/secretory-products-from-epicardial-adipose-tissue-from-patients-with-type-2-diabetes-impair-mitochondrial-%C3%AE-oxidation-in-cardiomyocytes-via-activation-of-the-cardiac-renin-angiotensin-system-and-induction-of-mir-208a
#16
Marcel Blumensatt, Pia Fahlbusch, Rebecca Hilgers, Marlies Bekaert, Daniella Herzfeld de Wiza, Payam Akhyari, Johannes B Ruige, D Margriet Ouwens
Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin-angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study investigated whether cardiomyocyte dysfunction induced by conditioned media (CM) from EAT-T2D involves activation of the RAS/miR-208a pathway...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27189278/metabolic-pathway-signatures-associated-with-urinary-metabolite-biomarkers-differentiate-bladder-cancer-patients-from-healthy-controls
#17
Won Tae Kim, Seok Joong Yun, Chunri Yan, Pildu Jeong, Ye Hwan Kim, Il Seok Lee, Ho Won Kang, Sunghyouk Park, Sung Kwon Moon, Yung Hyun Choi, Young Deuk Choi, Isaac Yi Kim, Jayoung Kim, Wun Jae Kim
PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed...
July 2016: Yonsei Medical Journal
https://www.readbyqxmd.com/read/26784927/glucose-alters-per2-rhythmicity-independent-of-ampk-whereas-ampk-inhibitor-compound-c-causes-profound-repression-of-clock-genes-and-agrp-in-mhypoe-37-hypothalamic-neurons
#18
Johanneke E Oosterman, Denise D Belsham
Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5...
2016: PloS One
https://www.readbyqxmd.com/read/26725848/genetic-alterations-in-fatty-acid-transport-and-metabolism-genes-are-associated-with-metastatic-progression-and-poor-prognosis-of-human-cancers
#19
Aritro Nath, Christina Chan
Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets...
January 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26708865/carnitine-palmitoyltransferase-1c-from-cognition-to-cancer
#20
REVIEW
Núria Casals, Victor Zammit, Laura Herrero, Rut Fadó, Rosalía Rodríguez-Rodríguez, Dolors Serra
Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression. Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with l-carnitine and acyl-CoA esters...
January 2016: Progress in Lipid Research
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