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https://www.readbyqxmd.com/read/28108289/negative-feedback-regulation-between-microrna-let-7g-and-lox-1-mediated-hypoxia-induced-pasmcs-proliferation
#1
Wei-Fang Zhang, Tian-Tian Zhu, You-Wen Xiong, Ai-Zhen Xiong, Xiao-Yue Ge, Chang-Ping Hu, Zheng Zhang
BACKGROUND: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressed c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28106301/uxt-is-a-lox-pp-interacting-protein-that-modulates-estrogen-receptor-alpha-activity-in-breast-cancer-cells
#2
Nuria Sánchez-Morgan, Kathrin H Kirsch, Philip C Trackman, Gail E Sonenshein
The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously eXpressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28101475/anticonvulsive-effects-of-licofelone-on-status-epilepticus-induced-by-lithium-pilocarpine-in-wistar-rats-a-role-for-inducible-nitric-oxide-synthase
#3
Seyyed Majid Eslami, Mohammad Mobin Moradi, Mehdi Ghasemi, Ahmad Reza Dehpour
BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE...
December 2016: Journal of Epilepsy Research
https://www.readbyqxmd.com/read/28098753/reagent-less-and-robust-biosensor-for-direct-determination-of-lactate-in-food-samples
#4
Iria Bravo, Mónica Revenga-Parra, Félix Pariente, Encarnación Lorenzo
Lactic acid is a relevant analyte in the food industry, since it affects the flavor, freshness, and storage quality of several products, such as milk and dairy products, juices, or wines. It is the product of lactose or malo-lactic fermentation. In this work, we developed a lactate biosensor based on the immobilization of lactate oxidase (LOx) onto N,N'-Bis(3,4-dihydroxybenzylidene) -1,2-diaminobenzene Schiff base tetradentate ligand-modified gold nanoparticles (3,4DHS-AuNPs) deposited onto screen-printed carbon electrodes, which exhibit a potent electrocatalytic effect towards hydrogen peroxide oxidation/reduction...
January 13, 2017: Sensors
https://www.readbyqxmd.com/read/28096231/roles-of-5-lipoxygenase-and-cyclooxygenase-2-in-the-biosynthesis-of-hemiketals-e2-and-d2-by-activated-human-leukocytes
#5
Juan A Giménez-Bastida, Takahiro Shibata, Koji Uchida, Claus Schneider
The 2 hemiketal (HK) eicosanoids HKD2 and HKE2 are the major products of the biosynthetic crossover of the 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) pathways. HKs result from the rearrangement of a di-endoperoxide intermediate formed in the COX-2-dependent oxygenation of 5S-hydroxyeicosatetraenoic acid (5S-HETE). We analyzed HK biosynthesis in human leukocytes stimulated ex vivo and defined the biosynthetic roles of 5-LOX and COX-2, using inhibitors and incubations with exogenous substrates. Activation of leukocytes with LPS followed by treatment with the calcium ionophore A23187 resulted in the formation of PGE2, 5-HETE, and LTB4 as the principal metabolites of COX-2 and 5-LOX, respectively...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096061/connexin37-deficiency-alters-organic-bone-matrix-cortical-bone-geometry-and-increases-wnt-%C3%AE-catenin-signaling
#6
Rafael Pacheco-Costa, Jay R Kadakia, Emily G Atkinson, Joseph M Wallace, Lilian I Plotkin, Rejane D Reginato
Deletion of connexin (Cx) 37 in mice leads to increased cancellous bone mass due to defective osteoclast differentiation. Paradoxically; however, Cx37-deficient mice exhibit reduced cortical thickness accompanied by higher bone strength, suggesting a contribution of Cx37 to bone matrix composition. Thus, we investigated whether global deletion of Cx37 alters the composition of organic bone extracellular matrix. Five-month-old Cx37(-/-) mice exhibited increased marrow cavity area, and periosteal and endocortical bone surface resulting in higher total area in tibia compared to Cx37(+/+) control mice...
January 13, 2017: Bone
https://www.readbyqxmd.com/read/28095362/in-vivo-modulation-of-lps-induced-leukotrienes-generation-and-oxidative-stress-by-sesame-lignans
#7
Puttaraju Srikantamurthy Yashaswini, Bettadahalli Sadashivaiah, Talahalli Ravichandra Ramaprasad, Sridevi Annapurna Singh
The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA2 (61 and 56%), 5-LOX (44 and 51%), BLT-1(32 and 35%) and LTC4 synthase (49 and 50%), respectively, in liver homogenate...
December 29, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28093240/the-crystal-structure-of-pseudomonas-aeruginosa-lipoxygenase-ala420gly-mutant-explains-the-improved-oxygen-affinity-and-the-altered-reaction-specificity
#8
Jacqueline Kalms, Swathi Banthiya, Etienne Galemou Yoga, Mats Hamberg, Hermann-Georg Holzhutter, Hartmut Kuhn, Patrick Scheerer
Secreted LOX from Pseudomonas aeruginosa (PA-LOX) has previously been identified as arachidonic acid 15S-lipoxygenating enzyme. Here we report that the substitution of Ala420Gly in PA-LOX leads to an enzyme variant with pronounced dual specificity favoring arachidonic acid 11R-oxygenation. When compared with other LOX-isoforms the oxygen affinity of wild-type PA-LOX is 1-2 orders of magnitude lower (oxygen Km of 0.4mM) but Ala420Gly exchange improved the oxygen affinity (oxygen Km of 0.2mM). Experiments with stereo-specifically deuterated linoleic acid indicated that the formation of both 13S- and 9R-HpODE involves abstraction of the proS-hydrogen from C11 of the fatty acid backbone...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28091585/microrna-19b-is-a-potential-biomarker-of-increased-myocardial-collagen-cross-linking-in-patients-with-aortic-stenosis-and-heart-failure
#9
Javier Beaumont, Begoña López, Susana Ravassa, Nerea Hermida, Gorka San José, Idoia Gallego, Félix Valencia, Juan José Gómez-Doblas, Eduardo de Teresa, Javier Díez, Arantxa González
This study analyzed the potential associations of 7 myocardial fibrosis-related microRNAs with the quality of the collagen network (e.g., the degree of collagen fibril cross-linking or CCL) and the enzyme lysyl oxidase (LOX) responsible for CCL in 28 patients with severe aortic stenosis (AS) of whom 46% had a diagnosis of chronic heart failure (HF). MicroRNA expression was analyzed in myocardial and blood samples. From the studied microRNAs only miR-19b presented a direct correlation (p < 0.05) between serum and myocardium...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090567/the-rna-polymerase-iii-subunit-polr3b-is-required-for-the-maintenance-of-small-intestinal-crypts-in-mice
#10
Julia Kieckhaefer, Sabina Lukovac, Diana Z Ye, Dolim Lee, Danielle J Beetler, Michael Pack, Klaus H Kaestner
BACKGROUND & AIMS: The continuously self-renewing mammalian intestinal epithelium, with high cellular turnover, depends on adequate protein synthesis for its proliferative capacity. RNA polymerase III activity is closely related to cellular growth and proliferation. Here, we studied the role of Polr3b, a large RNA polymerase III subunit, in the mammalian intestinal epithelium. METHODS: We derived mice with an intestinal epithelium-specific hypomorphic mutation of the Polr3b gene, using VillinCre-mediated gene ablation...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28088519/phytochemicals-as-multi-target-inhibitors-of-the-inflammatory-pathway-a-modeling-and-experimental-study
#11
Nisha S Devi, Meera Ramanan, Padmapriya Paragi-Vedanthi, Mukesh Doble
The arachidonic acid pathway consists of several enzymes and targeting them is favored for developing anti-inflammatory drugs. However, till date the current drugs are generally active against a single target, leading to undesirable side-effects. Phytochemicals are known to inhibit multiple targets simultaneously and hence, an attempt is made here to investigate their suitability. A pharmacophore based study is performed with three sets of reported phytochemicals namely, dual 5-LOX/mPGES1, alkaloids and FLAP inhibitors...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28077158/ccl2-driven-inflammation-increases-mammary-gland-stromal-density-and-cancer-susceptibility-in-a-transgenic-mouse-model
#12
Xuan Sun, Danielle J Glynn, Leigh J Hodson, Cecilia Huo, Kara Britt, Erik W Thompson, Lucy Woolford, Andreas Evdokiou, Jeffrey W Pollard, Sarah A Robertson, Wendy V Ingman
BACKGROUND: Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. METHODS: Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter...
January 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28076846/effect-of-trp53-gene-deficiency-on-brain-injury-after-neonatal-hypoxia-ischemia
#13
Ana A Baburamani, Kristina S Sobotka, Regina Vontell, Carina Mallard, Veena G Supramaniam, Claire Thornton, Henrik Hagberg
Hypoxia-ischemia (HI) can result in permanent life-long injuries such as motor and cognitive deficits. In response to cellular stressors such as hypoxia, tumor suppressor protein p53 is activated, potently initiating apoptosis and promoting Bax-dependent mitochondrial outer membrane permeabilization. The aim of this study was to investigate the effect of Trp53 genetic inhibition on injury development in the immature brain following HI. HI (50 min or 60 min) was induced at postnatal day 9 (PND9) in Trp53 heterozygote (het) and wild type (WT) mice...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28072480/free-fatty-acids-induce-autophagy-and-lox-1-upregulation-in-cultured-aortic-vascular-smooth-muscle-cells
#14
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Elevation of free fatty acids (FFAs) is known to affect microvascular function and contribute to obesity-associated insulin resistance, hypertension, and microangiopathy. Proliferative and synthetic vascular smooth muscle cells (VSMCs) increase intimal thickness and destabilize atheromatous plaques. This study aimed to investigate whether saturated palmitic acid (PA) and monounsaturated oleic acid (OA) modulate autophagy activity, cell proliferation, and vascular tissue remodeling in an aortic VSMC cell line...
November 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28069825/intravenous-anesthetic-propofol-binds-to-5-lipoxygenase-and-attenuates-leukotriene-b4-production
#15
Toshiaki Okuno, Sophia Koutsogiannaki, Mai Ohba, Matthew Chamberlain, Weiming Bu, Fu-Yan Lin, Roderic G Eckenhoff, Takehiko Yokomizo, Koichi Yuki
Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28065600/lysyl-oxidase-3-is-a-dual-specificity-enzyme-involved-in-stat3-deacetylation-and-deacetylimination-modulation
#16
Li Ma, Chao Huang, Xiong-Jun Wang, Dazhuan Eric Xin, Li-Shun Wang, Quanli C Zou, Ya-Nan S Zhang, Min-Dian Tan, Yu-Mei Wang, Ting C Zhao, Devasis Chatterjee, Rachel A Altura, Chuangui Wang, Yan S Xu, Jing-Hua Yang, Yong-Sheng Fan, Bao-Hui Han, Jianmin Si, Xiaoren Zhang, Jinke Cheng, Zhijie Chang, Y Eugene Chin
In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28060764/loxl4-knockdown-enhances-tumor-growth-and-lung-metastasis-through-collagen-dependent-extracellular-matrix-changes-in-triple-negative-breast-cancer
#17
Sul Ki Choi, Hoe Suk Kim, Tiefeng Jin, Woo Kyung Moon
Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels...
2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059043/natural-products-as-anticancerous-therapeutic-molecules-with-special-reference-to-enzymatic-targets-topoisomerase-cox-lox-and-aromatase
#18
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra Dwivedi
Cancer, characterized by uncontrolled growth and proliferation of cells, is affecting millions of people every year and estimated as the second leading cause of death. Its successful treatment yet remains a challenge due to the lack of selectivity, toxicity and the development of multi-drug resistant cells to the currently available drugs. Plant derived natural products hold great promise for discovery and development of new pharmaceuticals against cancer as evident by the fact that out of 121 drugs prescribed for cancer treatment till date, 90 are derived from plant sources...
January 5, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28057806/12-15-lipoxygenase-inhibition-or-knockout-reduces-warfarin-associated-hemorrhagic-transformation-after-experimental-stroke
#19
Yu Liu, Yi Zheng, Hulya Karatas, Xiaoying Wang, Christian Foerch, Eng H Lo, Klaus van Leyen
BACKGROUND AND PURPOSE: For stroke prevention, patients with atrial fibrillation typically receive oral anticoagulation. The commonly used anticoagulant warfarin increases the risk of hemorrhagic transformation (HT) when a stroke occurs; tissue-type plasminogen activator treatment is therefore restricted in these patients. This study was designed to test the hypothesis that 12/15-lipoxygenase (12/15-LOX) inhibition would reduce HT in warfarin-treated mice subjected to experimental stroke...
January 5, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28053825/bioactive-flavonoids-and-catechols-as-hif1-and-nrf2-protein-stabilizers-implications-for-parkinson-s-disease
#20
Natalya A Smirnova, Navneet Ammal Kaidery, Dmitry M Hushpulian, Ilay I Rakhman, Andrey A Poloznikov, Vladimir I Tishkov, Saravanan S Karuppagounder, Irina N Gaisina, Anton Pekcec, Klaus Van Leyen, Sergey V Kazakov, Lichuan Yang, Bobby Thomas, Rajiv R Ratan, Irina G Gazaryan
Flavonoids are known to trigger the intrinsic genetic adaptive programs to hypoxic or oxidative stress via estrogen receptor engagement or upstream kinase activation. To reveal specific structural requirements for direct stabilization of the transcription factors responsible for triggering the antihypoxic and antioxidant programs, we studied flavones, isoflavones and catechols including dihydroxybenzoate, didox, levodopa, and nordihydroguaiaretic acid (NDGA), using novel luciferase-based reporters specific for the first step in HIF1 or Nrf2 protein stabilization...
December 2016: Aging and Disease
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