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https://www.readbyqxmd.com/read/29223589/breakthroughs-in-neuroactive-steroid-drug-discovery
#1
REVIEW
Maria-Jesus Blanco, Daniel La, Quinn Coughlin, Caitlin A Newman, Andrew M Griffin, Boyd L Harrison, Francesco G Salituro
Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are effective modulators of multiple signaling pathways including receptors for the γ-aminobutyric acid A (GABAA) and glutamate, in particular N-methyl-d-aspartate (NMDA). These receptors are the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS), and there is growing evidence suggesting that dysregulation of neurosteroid production plays a role in numerous neurological disorders. The significant unmet medical need for treatment of CNS disorders has increased the interest for these types of compounds...
December 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29215550/poly-%C3%AE-glutamic-acid-synthesis-gene-regulation-phylogenetic-relationships-and-role-in-fermentation
#2
REVIEW
Yi-Huang Hsueh, Kai-Yao Huang, Sikhumbuzo Charles Kunene, Tzong-Yi Lee
Poly-γ-glutamic acid (γ-PGA) is a biodegradable biopolymer produced by several bacteria, including Bacillus subtilis and other Bacillus species; it has good biocompatibility, is non-toxic, and has various potential biological applications in the food, pharmaceutical, cosmetic, and other industries. In this review, we have described the mechanisms of γ-PGA synthesis and gene regulation, its role in fermentation, and the phylogenetic relationships among various pgsBCAE, a biosynthesis gene cluster of γ-PGA, and pgdS, a degradation gene of γ-PGA...
December 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29215197/enrichment-of-gamma-aminobutyric-acid-in-bean-sprouts-exploring-biosynthesis-of-plant-metabolite-using-common-household-reagents
#3
Theerasak Rojanarata, Samarwadee Plianwong, Praneet Opanasopit, Tanasait Ngawhirunpat
The enrichment of plant foods with gamma-aminobutyric acid (GABA) is currently an interesting issue in the field of nutraceuticals and can be used as an experiment for upper-division undergraduate students. Here, an interdisciplinary hands-on experiment to produce GABA-enriched mung bean sprouts using common household reagents is described. Based on the GABA biosynthesis pathways, two key factors, being the availability of l-glutamic acid and the acidification of the germination environment, were chosen for the study of the effects on the enhancement of GABA levels...
December 7, 2017: Biochemistry and Molecular Biology Education
https://www.readbyqxmd.com/read/29212737/astrocytic-lrp4-low-density-lipoprotein-receptor-related-protein-4-contributes-to-ischemia-induced-brain-injury-by-regulating-atp-release-and-adenosine-a2ar-adenosine-a2a-receptor-signaling
#4
Xin-Chun Ye, Jin-Xia Hu, Lei Li, Qiang Li, Fu-Lei Tang, Sen Lin, Dong Sun, Xiang-Dong Sun, Gui-Yun Cui, Lin Mei, Wen-Cheng Xiong
BACKGROUND AND PURPOSE: Lrp4 (low-density lipoprotein receptor-related protein 4) is predominantly expressed in astrocytes, where it regulates glutamatergic neurotransmission by suppressing ATP release. Here, we investigated Lrp4's function in ischemia/stroke-induced brain injury response, which includes glutamate-induced neuronal death and reactive astrogliosis. METHODS: The brain-specific Lrp4 conditional knockout mice (Lrp4GFAP-Cre), astrocytic-specific Lrp4 conditional knockout mice (Lrp4GFAP-creER), and their control mice (Lrp4f/f) were subjected to photothrombotic ischemia and the transient middle cerebral artery occlusion...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29211784/urinary-metabolomic-analysis-to-identify-preterm-neonates-exposed-to-histological-chorioamnionitis-a-pilot-study
#5
Claudia Fattuoni, Carlo Pietrasanta, Lorenza Pugni, Andrea Ronchi, Francesco Palmas, Luigi Barberini, Angelica Dessì, Roberta Pintus, Vassilios Fanos, Antonio Noto, Fabio Mosca
OBJECTIVE: Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA...
2017: PloS One
https://www.readbyqxmd.com/read/29204887/molecular-evolution-of-an-oligomeric-biocatalyst-functioning-in-lysine-biosynthesis
#6
REVIEW
Tatiana P Soares da Costa, Belinda M Abbott, Anthony R Gendall, Santosh Panjikar, Matthew A Perugini
Dihydrodipicolinate synthase (DHDPS) is critical to the production of lysine through the diaminopimelate (DAP) pathway. Elucidation of the function, regulation and structure of this key class I aldolase has been the focus of considerable study in recent years, given that the dapA gene encoding DHDPS has been found to be essential to bacteria and plants. Allosteric inhibition by lysine is observed for DHDPS from plants and some bacterial species, the latter requiring a histidine or glutamate at position 56 (Escherichia coli numbering) over a basic amino acid...
December 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29204750/protective-effects-of-fisetin-against-6-ohda-induced-apoptosis-by-activation-of-pi3k-akt-signaling-in-human-neuroblastoma-sh-sy5y-cells
#7
Ryoko Watanabe, Takumi Kurose, Yuta Morishige, Ko Fujimori
6-Hydroxydopamine (6-OHDA) induces the production of reactive oxygen species (ROS) that are associated with various neurodegenerative diseases such as Parkinson's disease. 3,3',4',7-Tetrahydroxyflavone (fisetin), a plant flavonoid has a variety of physiological effects such as antioxidant activity. In this study, we investigated the molecular mechanism of the neuroprotective effects of fisetin against 6-OHDA-induced cell death in human neuroblastoma SH-SY5Y cells. 6-OHDA-mediated cell toxicity was reduced in a fisetin concentration-dependent manner...
December 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29202856/sulfosuccinimidyl-oleate-sodium-is-neuroprotective-and-alleviates-stroke-induced-neuroinflammation
#8
Hiramani Dhungana, Mikko T Huuskonen, Merja Jaronen, Sighild Lemarchant, Humair Ali, Velta Keksa-Goldsteine, Gundars Goldsteins, Katja M Kanninen, Jari Koistinaho, Tarja Malm
BACKGROUND: Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage. METHODS: By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO)...
December 4, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29200201/the-actions-of-nme1-ndpk-a-and-nme2-ndpk-b-as-protein-kinases
#9
Paul V Attwood, Richmond Muimo
Nucleoside diphosphate kinases (NDPKs) are multifunctional proteins encoded by the nme (non-metastatic cells) genes, also called NM23. NDPKs catalyze the transfer of γ-phosphate from nucleoside triphosphates to nucleoside diphosphates by a ping-pong mechanism involving the formation of a high-energy phosphohistidine intermediate. Growing evidence shows that NDPKs, particularly NDPK-B, can additionally act as a protein histidine kinase. Protein kinases and phosphatases that regulate reversible O-phosphorylation of serine, threonine, and tyrosine residues have been studied extensively in many organisms...
December 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29198954/metabolic-reprogramming-of-hydrogenosomal-amino-acids-in-trichomonas-vaginalis-under-glucose-restriction
#10
Kuo-Yang Huang, Seow-Chin Ong, Chih-Ching Wu, Chia-Wei Hsu, Hsin-Chung Lin, Yi-Kai Fang, Wei-Hung Cheng, Po-Jung Huang, Cheng-Hsun Chiu, Petrus Tang
BACKGROUND: Glucose is the major energy source that is converted to pyruvate for ATP generation in the trichomonad hydrogenosome. Under glucose restriction (GR), the regulation of amino acids metabolism is crucial for trichomonad growth and survival. RNA-sequencing (RNA-seq) analysis has been used to identify differentially expressed genes in Trichomonas vaginalis under GR, leading to significant advances in understanding adaptive responses of amino acid metabolism to GR. However, the levels of amino acid metabolites modulated by GR are unknown in T...
November 21, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/29196951/behavioral-and-biochemical-effects-of-n-acetylcysteine-in-zebrafish-acutely-exposed-to-ethanol
#11
Ricieri Mocelin, Matheus Marcon, Simone D'ambros, Ana P Herrmann, Alex Sander da Rosa Araujo, Angelo Piato
Alcohol hangover refers to unpleasant symptoms experienced as a direct consequence of a binge drinking episode. The effects observed in this condition are related to the increase in alcohol metabolites and imbalance in oxidative status. N-acetylcysteine (NAC) is a mucolytic agent and an antidote for paracetamol overdose. Preclinical and clinical studies have shown that NAC is a multi-target drug acting through neuroprotective, antioxidant and neurotrophic mechanisms as well as a glutamate modulator. The aim of this study was to investigate the effects of NAC in zebrafish acutely exposed to ethanol (EtOH)...
December 1, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29196105/asiatic-acid-ameliorates-hepatic-ischemia-reperfusion-injury-in-rats-via-mitochondria-targeted-protective-mechanism
#12
Yapeng Lu, Huiwen Kan, Ying Wang, Dan Wang, Xueting Wang, Jing Gao, Li Zhu
It has been proved that asiatic acid (AA) directly targets mitochondria and acts as a mild mitochondrial uncoupler. In this study, we aim to investigate the protective effects of AA against ischemia/reperfusion (I/R)-induced liver injury in rats and some underlying mechanisms involved were elucidated. The results showed that 50mg/kg AA pre-treatment significantly reduced I/R-induced liver damage, characterized by the decreased release of aspartate aminotransferase (AST) and TNF-α. Furthermore, AA pre-treatment dramatically inhibited the production of MDA and increased the hepatic SOD, catalase activities and GSH levels in liver tissue of I/R rats which indicated that AA ameliorated I/R-induced liver damage by reducing oxidative stress...
November 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29191950/metabolic-re-patterning-in-copd-airway-smooth-muscle-cells
#13
Charalambos Michaeloudes, Chih-Hsi Kuo, Gulam Haji, Donna K Finch, Andrew J Halayko, Paul Kirkham, Kian Fan Chung, Ian M Adcock
Chronic obstructive pulmonary disease (COPD) airways are characterised by thickening of airway smooth muscle, partly due to airway smooth muscle cell (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth. We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth.We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy nonsmokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29190426/neuroprotective-effects-of-acetylcholinesterase-inhibitory-peptides-from-anchovy-coilia-mystus-against-glutamate-induced-toxicity-in-pc12-cells
#14
Tiantian Zhao, Guowan Su, Shuguang Wang, Qi Zhang, Jianan Zhang, Lin Zheng, Bao-Guo Sun, Mouming Zhao
Ameliorations of cholinergic system dysfunction and oxidative stress in neurodegenerative diseases were main approaches to improve memory disorder. Our previous investigation showed that anchovy protein hydrolysate (APH) could attenuate scopolamine-induced memory deficits in mice by regulating acetylcholinesterase (AChE) activity. Therefore, peptides with AChE inhibitory activity in APH were explored and identified in this study, and their possible neuroprotective mechanisms on glutamate induced apoptosis in PC12 were also elucidated...
November 30, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29188330/metabolic-pathway-of-6-aminohexanoate-in-the-nylon-oligomer-degrading-bacterium-arthrobacter-sp-ki72-identification-of-the-enzymes-responsible-for-the-conversion-of-6-aminohexanoate-to-adipate
#15
Ikki Takehara, Tsubasa Fujii, Yuuki Tanimoto, Dai-Ichiro Kato, Masahiro Takeo, Seiji Negoro
Arthrobacter sp. strain KI72 grows on a 6-aminohexanoate oligomer, which is a by-product of nylon-6 manufacturing, as a sole source of carbon and nitrogen. We cloned the two genes, nylD 1 and nylE 1 , responsible for 6-aminohexanoate metabolism on the basis of the draft genomic DNA sequence of strain KI72. We amplified the DNA fragments that encode these genes by polymerase chain reaction using a synthetic primer DNA homologous to the 4-aminobutyrate metabolic enzymes. We inserted the amplified DNA fragments into the expression vector pColdI in Escherichia coli, purified the His-tagged enzymes to homogeneity, and performed biochemical studies...
November 29, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29181726/the-inhibition-of-polyamine-biosynthesis-weakens-the-drought-tolerance-in-white-clover-trifolium-repens-associated-with-the-alteration-of-extensive-proteins
#16
Zhou Li, Yan Zhang, Dandan Peng, Yan Peng, Xinquan Zhang, Xiao Ma, Linkai Huang, Yanhong Yan
Changes of endogenous polyamine (PA) levels could be a key adaptive response to drought in plants. White clover pretreated with or without dicyclohexylamine (DCHA), an inhibitor of PA biosynthesis, was subjected to drought stress induced by 18% polyethylene glycol 6000 for 8 days in controlled growth chambers. Results showed that drought stress significantly increased endogenous PA content, whereas DCHA significantly decreased PA accumulation under drought stress. The attenuate PA biosynthesis was unfavorable for plant growth and drought tolerance, as reflected by significantly lower relative water content, relative growth rate, instantaneous water use efficiency, and cell membrane stability in leaves in response to drought...
November 28, 2017: Protoplasma
https://www.readbyqxmd.com/read/29181662/inhibition-of-the-expression-of-inducible-no-synthase-by-neuroactive-amino-acid-derivatives-phenibut-and-glufimet-in-vitro-and-ex-vivo
#17
A V Borisov, I I Prokofiev, I S Mokrousov, V N Perfilova, I N Tyurenkov
The effects of glufimet and phenibut (glutamic acid and GABA derivatives, respectively) on concentration of inducible NO synthase and cGMP in LPS-activated mouse peritoneal macrophages and on NO end products in their culture medium were examined in vitro and ex vivo. Addition of LPS into culture medium elevated concentration of NO metabolites in this medium and increased concentration of inducible NO synthase and cGMP in the lysates of peritoneal macrophages, whereas incubation of the cells with examined agents applied at concentration of 10-5 M diminished these indices...
November 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29177886/production-of-poly-%C3%AE-glutamic-acid-by-a-thermotolerant-glutamate-independent-strain-and-comparative-analysis-of-the-glutamate-dependent-difference
#18
Wei Zeng, Guiguang Chen, Ye Guo, Bin Zhang, Mengna Dong, Yange Wu, Jun Wang, Zhiqun Che, Zhiqun Liang
Poly-γ-glutamic acid (γ-PGA) is a promising microbial polymer with wide applications in industry, agriculture and medicine. In this study, a novel glutamate-independent γ-PGA producing strain with thermotolerant characteristics was isolated and identified as Bacillus subtilis GXG-5, then its product was also characterized. The fermentation process was optimized by single-factor tests, and results showed that high temperature (50 °C) was especially suitable for the γ-PGA production by GXG-5. The γ-PGA yield reached 19...
November 25, 2017: AMB Express
https://www.readbyqxmd.com/read/29175697/in-vivo-study-of-erysolin-metabolic-profile-by-ultra-high-performance-liquid-chromatography-coupleded-to-fourier-transform-ion-cyclotron-resonance-mass-spectrometry
#19
Binglong Li, Hui Zhou, Guochun Yang, Fei Han, Yanting Li, Yongfeng Gao, Jinwei Gao, Feng Zhang, Lixin Sun
An ultra high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) method was developed for the first time to study the in vivo metabolism of erysolin, a compound derived from cruciferous plants which has a definite effect of anti-tumor and anti-nerve injury. In this research, the chromatographic separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 mm×100mm, 1.7μm, Waters, USA) and eluted by a gradient program, the identification work was achieved on a Bruker ultra-high resolution spectrometer in positive ion mode...
November 16, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29167114/exocrine-pancreas-glutamate-secretion-help-to-sustain-enterocyte-nutritional-needs-under-protein-restriction
#20
Selene Araya, Evelyne Kuster, Dino Gluch, Luca Mariotta, Christian Lutz, Theresia V Reding, Rolf Graf, François Verrey, Simone M R Camargo
Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs and the potential role of the Gln-glutamate (Glu) cycle are unknown...
November 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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