keyword
MENU ▼
Read by QxMD icon Read
search

substrate inhibition

keyword
https://www.readbyqxmd.com/read/28722021/activation-of-the-gabaergic-parafacial-zone-maintains-sleep-and-counteracts-the-wake-promoting-action-of-the-psychostimulants-armodafinil-and-caffeine
#1
C Anaclet, K Griffith, P M Fuller
We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZ(Vgat)) neurons in behaving mice produces slow-wave-sleep (SWS), even in the absence of sleep deficit, suggesting that these neurons may represent, at least in part, a key cellular substrate underlying sleep drive. It remains however to be determined if PZ(Vgat) neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZ(Vgat) neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, armodafinil or caffeine...
July 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28720901/a-novel-connection-between-the-cell-wall-integrity-and-the-pka-pathways-regulates-cell-wall-stress-response-in-yeast
#2
Raúl García, Enrique Bravo, Sonia Diez-Muñiz, Cesar Nombela, Jose M Rodríguez-Peña, Javier Arroyo
Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#3
Jin Cheng, Feng Ye, Guorong Dan, Yuanpeng Zhao, Jiqing Zhao, Zhongmin Zou
N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme which solely repairs alkyl adduct on DNA directly. However, MGMT was detected to act as a protein cross-linked with DNA via alkylation in presence of HN2, and unexpectedly turned into a DNA damage enhancer in the form of MGMT-DNA cross-link (mDPC)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28719179/inhibition-of-human-class-i-vs-class-iii-phosphatidylinositol-3-kinases
#4
Matthew Hassett, Anna Sternberg, Paul David Roepe
Most investigations of phosphatidylinositol 3'-kinase (PI3K) drug inhibition have been via assays based on ADP appearance or ATP consumption (e.g. Liu, Q. et al. (2011) J. Med. Chem. 54, 1473-1480). However, at least some PI3K isoforms show basal ATPase activity in the absence of PI lipid substrate(s), which may complicate quantification of drug potency, isoform specificity of some drugs, and synergy for drug combinations. In this study, we probe the class I vs class III isoform specificity of a selected set of phosphatidylinositol 3'-kinase (PI3K) inhibitors using a simple, inexpensive, semi high-throughput assay that quantifies production of phosphatidylinositol 3'-phosphate (PI3P) from phosphatidylinositol (PI)...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28717819/atrophic-degeneration-of-cerebellum-impairs-both-the-reactive-and-the-proactive-control-of-movement-in-the-stop-signal-paradigm
#5
Giusy Olivito, Emiliano Brunamonti, Silvia Clausi, Pierpaolo Pani, Francesca R Chiricozzi, Margherita Giamundo, Marco Molinari, Maria Leggio, Stefano Ferraina
The cognitive control of movement suppression, including performance monitoring, is one of the core properties of the executive system. A complex cortical and subcortical network involving cerebral cortex, thalamus, subthalamus, and basal ganglia has been regarded as the neural substrate of inhibition of programmed movements. Using the countermanding task, a suitable tool to explore behavioral components of movement suppression, the contribution of the cerebellum in the proactive control and monitoring of voluntary action has been recently described in patients affected by focal lesions involving in particular the cerebellar dentate nucleus...
July 17, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#6
Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716944/potent-competitive-inhibition-of-human-ribonucleotide-reductase-by-a-nonnucleoside-small-molecule
#7
Md Faiz Ahmad, Intekhab Alam, Sarah E Huff, John Pink, Sheryl A Flanagan, Donna Shewach, Tessianna A Misko, Nancy L Oleinick, William E Harte, Rajesh Viswanathan, Michael E Harris, Chris Godfrey Dealwis
Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by additional effects, including DNA chain termination. The discovery of nonnucleoside, reversible, small-molecule inhibitors with greater specificity against hRRM1 is a key step in the development of more effective treatments for cancer...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716760/properties-of-purified-cyp2r1-in-a-reconstituted-membrane-environment-and-its-25-hydroxylation-of-20-hydroxyvitamin-d3
#8
Chloe Y S Cheng, Tae-Kang Kim, Saowanee Jeayeng, Andrzej T Slominski, Robert C Tuckey
Recent studies indicate that CYP2R1 is the major 25-hydroxylase catalyzing the first step in vitamin D activation. Since the catalytic properties of CYP2R1 have been poorly studied to date and it is a membrane protein, we examined the purified enzyme in a membrane environment. CYP2R1 was expressed in E. coli and purified by nickel affinity- and hydrophobic interaction-chromatography and assayed in a reconstituted membrane system comprising phospholipid vesicles plus purified human NADPH-P450 oxidoreductase...
July 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28715738/inhibition-of-ammonia-on-anaerobic-digestion-of-synthetic-coal-gasification-wastewater-and-recovery-using-struvite-precipitation
#9
Wei Wang, Xuesong Ren, Kai Yang, Zhenhu Hu, Shoujun Yuan
Coal gasification wastewater (CGW) contains very high concentrations of phenols and ammonia. However, the potential impact of ammonia on the anaerobic digestion of phenols remained unclear. Firstly, the methanogens and phenols degraders had a good tolerance up to 1gL(-1) of total ammonia nitrogen (TAN), but the substrate utilization rate for phenol, and specific methanogenic activity of sludge were decreased by 89% and 67% at 5g TAN L(-1), and 94% and 100% at 10g TAN L(-1), respectively. Secondly, the optimum struvite crystallization conditions (pH=8...
July 3, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#10
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28714293/research-highlights
#11
(no author information available yet)
In this issue, we highlight a report from Sack et al. on a mechanism linking fasting to inhibition of NLRP3 inflammasome activation, a study from Brodsky and colleagues on ERAD substrate recognition and Cdc48p-faciliated retrotranslocation, and a study from Shindou et al. on a role for DHA in maintaining disc morphology of retinal photoreceptor cells.
July 2017: FEBS Journal
https://www.readbyqxmd.com/read/28714243/regulation-of-the-activity-of-the-promoter-of-rna-induced-silencing-c3po
#12
Shriya Sahu, Leo Williams, Alberto Perez, Finly Philip, Giuseppe Caso, Walter Zurawsky, Suzanne Scarlata
RNA-induced silencing is a process which allows cells to regulate the synthesis of specific proteins. RNA silencing is promoted by the protein C3PO (component 3 of RISC). We have previously found that phospholipase Cβ, which increases intracellular calcium levels in response to specific G protein signals, inhibits C3PO activity towards certain genes. Understanding the parameters that control C3PO activity and which genes are impacted by G protein activation would help predict which genes are more vulnerable to down-regulation...
July 16, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28714209/biotransporting-self-assembled-nanofactories-using-polymer-vesicles-with-molecular-permeability-for-enzyme-prodrug-cancer-therapy
#13
Tomoki Nishimura, Yoshihiro Sasaki, Kazunari Akiyoshi
As "biotransporting nanofactories", in vivo therapeutic biocatalyst nanoreactors would enable encapsulated enzymes to transform inert prodrugs or neutralize toxic compounds at target disease sites. This would offer outstanding potential for next-generation therapeutic platforms, such as enzyme prodrug therapy. Designing such advanced materials has, however, proven challenging. Here, it is shown that self-assembled nanofactories formulate with polymeric vesicles with an intrinsically permeable membrane. The vesicles, CAPsomes, are composed of carbohydrate-b-poly(propylene glycol) and show molecular-weight-depended permeability...
July 17, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28714135/yap-suppresses-gluconeogenic-gene-expression-via-pgc1%C3%AE
#14
Yue Hu, Dong-Ju Shin, Hui Pan, Zhiqiang Lin, Jonathan M Dreyfuss, Fernando D Camargo, Ji Miao, Sudha B Biddinger
Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step towards understanding development, regeneration and cancer. The transcriptional regulator Yes-associated protein 1 (YAP) is a key regulator of liver size, development and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28713943/astragaloside-iv-downregulates-the-expression-of-mdr1-in-bel%C3%A2-7402-fu-human-hepatic-cancer-cells-by-inhibiting-the-jnk-c%C3%A2-jun-ap%C3%A2-1-signaling-pathway
#15
Pei-Pei Wang, Jia-Jie Luan, Wen-Ke Xu, Lin Wang, Du-Juan Xu, Chun-Yan Yang, Yan-Hong Zhu, Ya-Qin Wang
Previous studies demonstrated that astragaloside IV (ASIV) is a potential P‑glycoprotein (P‑gp)‑mediated multidrug resistance (MDR) reversal agent through mechanisms involving downregulation of the gene expression of mdr1. In order to investigate whether the c‑Jun N‑terminal kinase (JNK) signaling pathway is involved in the mechanism underlying ASIV‑induced downregulated the expression of mdr1, the present study used 5‑fluorouracil‑resistant Bel‑7402/FU human hepatic cancer cells as target cells...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713775/salivary-tick-cystatin-omc2-targets-lysosomal-cathepsins-s-and-c-in-human-dendritic-cells
#16
Tina Zavašnik-Bergant, Robert Vidmar, Andreja Sekirnik, Marko Fonović, Jiří Salát, Lenka Grunclová, Petr Kopáček, Boris Turk
To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28713276/structure-activity-relationships-of-pentacyclic-triterpenoids-as-potent-and-selective-inhibitors-against-human-carboxylesterase-1
#17
Li-Wei Zou, Tong-Yi Dou, Ping Wang, Wei Lei, Zi-Miao Weng, Jie Hou, Dan-Dan Wang, Yi-Ming Fan, Wei-Dong Zhang, Guang-Bo Ge, Ling Yang
Human carboxylesterase 1 (hCE1), one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs) were assayed using D-Luciferin methyl ester (DME) and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as specific optical substrate for hCE1, and hCE2, respectively...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712957/secretory-expression-of-%C3%AE-mannanase-from-bacillus-circulans-nt-6-7-in-lactobacillus-plantarum
#18
Kwankanit Intaratrukul, Sunee Nitisinprasert, Thu-Ha Nguyen, Dietmar Haltrich, Suttipun Keawsompong
The β-mannanase gene of Bacillus circulans NT 6.7 was successfully cloned in Lactobacillus plantarum WCFS1 using the pSIP403 expression vector and secreted to the supernatant rather than accumulated in the cells. The highest activity was achieved by controlling the pH at 6 during cultivation. Maximum mannanase activities detected in the supernatant and cell-free extract of 200 ml MRS broth were 8.2 and 0.86 U/ml, respectively. Enzyme activity in the supernatant increased to 27 U/ml by fermentation in a 5-L bioreactor with automatic pH control...
July 13, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28712845/dual-inhibitors-of-the-human-blood-brain-barrier-drug-efflux-transporters-p-glycoprotein-and-abcg2-based-on-the-antiviral-azidothymidine
#19
Hilda A Namanja-Magliano, Kelsey Bohn, Neha Agrawal, Meghan E Willoughby, Christine A Hrycyna, Jean Chmielewski
The brain provides a sanctuary site for HIV due, in part, to poor penetration of antiretroviral agents at the blood-brain barrier. This lack of penetration is partially attributed to drug efflux transporters such as P-glycoprotein (P-gp) and ABCG2. Inhibition of both ABCG2 and P-gp is critical for enhancing drug accumulation into the brain. In this work, we have developed a class of homodimers based on the HIV reverse transcriptase inhibitor azidothymidine (AZT) that effectively inhibits P-gp and ABCG2. These agents block transporter mediated efflux of the P-gp substrate calcein-AM and the ABCG2 substrate mitoxantrone...
July 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28712664/gsk3-and-its-interactions-with-the-pi3k-akt-mtor-signalling-network
#20
REVIEW
Miguel A Hermida, J Dinesh Kumar, Nick R Leslie
Glycogen Synthase Kinase-3 (GSK3 or GSK-3) is a promiscuous protein kinase and its phosphorylation of its diverse substrates has major influences on many areas of physiology and pathology, including cellular metabolism, lineage commitment and neuroscience. GSK3 was one of the first identified substrates of the heavily studied oncogenic kinase AKT, phosphorylation by which inhibits GSK3 activity via the formation of an autoinhibitory pseudosubstrate sequence. This has led to investigation of the role of GSK3 inhibition as a key component of the cellular responses to growth factors and insulin, which stimulate the class I PI 3-Kinases and in turn AKT activity and GSK3 phosphorylation...
June 27, 2017: Advances in Biological Regulation
keyword
keyword
33207
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"