Genomes and Genes
Experts and Doctors on enzyme inhibitors in United States
Locale: United States
Topic: enzyme inhibitors
Publications391 found, 100 shown here
- Cardounel A, Cui H, Samouilov A, Johnson W, Kearns P, Tsai A, et al. Evidence for the pathophysiological role of endogenous methylarginines in regulation of endothelial NO production and vascular function. J Biol Chem. 2007;282:879-87 pubmed..Thus, MAs are critical mediators of vascular dysfunction following vascular injury. ..
- Presley T, Vedam K, Velayutham M, Zweier J, Ilangovan G. Activation of Hsp90-eNOS and increased NO generation attenuate respiration of hypoxia-treated endothelial cells. Am J Physiol Cell Physiol. 2008;295:C1281-91 pubmed publisher..The present mechanistic insight will be helpful to understand the difference in the magnitude of endothelial dysfunction. ..
- Marusic S, Thakker P, Pelker J, Stedman N, Lee K, McKew J, et al. Blockade of cytosolic phospholipase A2 alpha prevents experimental autoimmune encephalomyelitis and diminishes development of Th1 and Th17 responses. J Neuroimmunol. 2008;204:29-37 pubmed publisher..Finally, blockade of cPLA2 alpha from the onset of clinical EAE reduced duration of EAE relapses. Therefore, cPLA2 alpha represents a potential therapeutic target for treatment of MS. ..
- Dykhuizen E, Kiessling L. Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite. Org Lett. 2009;11:193-6 pubmed publisher..The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site. ..
- Knuckley B, Causey C, Jones J, Bhatia M, Dreyton C, Osborne T, et al. Substrate specificity and kinetic studies of PADs 1, 3, and 4 identify potent and selective inhibitors of protein arginine deiminase 3. Biochemistry. 2010;49:4852-63 pubmed publisher..Additionally, the substrate specificity studies provided critical information that aided the identification of PAD3-selective inhibitors. These compounds, denoted F4- and Cl4-amidine, are the most potent PAD3 inhibitors ever described. ..
- Kumar R, Hu F, Sannigrahi P, Jung S, Ragauskas A, Wyman C. Carbohydrate derived-pseudo-lignin can retard cellulose biological conversion. Biotechnol Bioeng. 2013;110:737-53 pubmed publisher..The drop in cellulose conversion was higher than realized for cellulase inhibition by xylooligomers reported previously. Plausible mechanisms are discussed to explain the observed reductions in cellulose conversions. ..
- Wertheimer E, Krapf D, de la Vega Beltrán J, Sanchez Cardenas C, Navarrete F, Haddad D, et al. Compartmentalization of distinct cAMP signaling pathways in mammalian sperm. J Biol Chem. 2013;288:35307-20 pubmed publisher..Altogether, these data suggest that cAMP pathways are compartmentalized in sperm, with Gs and tmAC in the head and Adcy10 and PKA in the flagellum. ..
- Palmer S, Altan M, Denis D, Tos E, Gotteland J, Osteen K, et al. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016;23:11-23 pubmed publisher..c-Jun N-terminal kinase inhibition mediated a comprehensive reduction in cytokine secretion and moreover was able to overcome PR resistance. ..
- Saggu S, Hung H, Quiogue G, Lemasters J, Nieminen A. Lysosomal signaling enhances mitochondria-mediated photodynamic therapy in A431 cancer cells: role of iron. Photochem Photobiol. 2012;88:461-8 pubmed publisher..These results support the conclusion that chelatable iron stored in the lysosomes enhances the efficacy of bafilomycin-mediated PDT and that lysosomal disruption augments PDT with Pc 4. ..
- Minderman H, Wrzosek C, Cao S, Utsugi T, Kobunai T, Yamada Y, et al. Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-103 and activity against (multi)drug resistant cells. Cancer Chemother Pharmacol. 2000;45:78-84 pubmed
- Davidson G, Clugston S, Honek J, Maroney M. An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications. Biochemistry. 2001;40:4569-82 pubmed..This leads to an anionic complex, which is consistent with an observed 1.7 eV decrease in the Ni K-edge energy. Plausible reaction mechanisms for Ni-GlxI are discussed in light of the structural information available. ..
- Gibbs S, Becker A, Hardy R, Truman J. Soluble guanylate cyclase is required during development for visual system function in Drosophila. J Neurosci. 2001;21:7705-14 pubmed..We propose that diminished sGC activity in the visual system during development causes inappropriate or inadequate formation of first-order retinal synapses, leading to defects in visual system function and visually mediated behavior. ..
- Sevlever D, Mann K, Medof M. Differential effect of 1,10-phenanthroline on mammalian, yeast, and parasite glycosylphosphatidylinositol anchor synthesis. Biochem Biophys Res Commun. 2001;288:1112-8 pubmed..In contrast to mammals and yeast, the synthesis of GPIs in T. brucei is not affected by PNT. Our results indicate that the T. brucei GPI-PET could be a potential target for antiparasitic drugs. ..
- Scherer E, Herzog M, Wangemann P. Endothelin-1-induced vasospasms of spiral modiolar artery are mediated by rho-kinase-induced Ca(2+) sensitization of contractile apparatus and reversed by calcitonin gene-related Peptide. Stroke. 2002;33:2965-71 pubmed
- Dowdy S, Mariani A, Janknecht R. HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. J Biol Chem. 2003;278:44377-84 pubmed..This suggests that attenuation of TGF-beta signaling by activating Smad7 transcription may proceed not only through TGF-beta receptor-regulated Smad proteins but also through an independent pathway involving ER81 and TAK1. ..
- Megerian C. Diameter of the cochlear nerve in endolymphatic hydrops: implications for the etiology of hearing loss in Ménière's disease. Laryngoscope. 2005;115:1525-35 pubmed
- Wang H, Yuan G, Prabhakar N, Boswell M, Katz D. Secretion of brain-derived neurotrophic factor from PC12 cells in response to oxidative stress requires autocrine dopamine signaling. J Neurochem. 2006;96:694-705 pubmed..These data indicate that oxidative stress can stimulate BDNF release through an autocrine or paracrine loop that requires dopamine receptor activation. ..
- Chen G, Kittler J, Moss S, Yan Z. Dopamine D3 receptors regulate GABAA receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens. J Neurosci. 2006;26:2513-21 pubmed..Together, our results suggest that D3 receptor activation suppresses the efficacy of inhibitory synaptic transmission in NAc by increasing the phospho-dependent endocytosis of GABAA receptors. ..
- Fechtner R, Khouri A, Figueroa E, Ramirez M, Federico M, Dewey S, et al. Short-term treatment of cocaine and/or methamphetamine abuse with vigabatrin: ocular safety pilot results. Arch Ophthalmol. 2006;124:1257-62 pubmed..To evaluate the ocular safety of short-term use of vigabatrin to treat cocaine and/or methamphetamine addiction...
- Sullivan S, Holyoak T. Structures of rat cytosolic PEPCK: insight into the mechanism of phosphorylation and decarboxylation of oxaloacetic acid. Biochemistry. 2007;46:10078-88 pubmed..Last, the structures illustrate a correlation between conformational changes in the P-loop, the nucleotide binding site, and the active site lid that are important for catalysis. ..
- Nie D, Guo Y, Yang D, Tang Y, Chen Y, Wang M, et al. Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Cancer Res. 2008;68:115-21 pubmed publisher..Taken together, the data suggest that TPs are expressed in prostate cancer and activation of TPs regulates prostate cancer cell motility and cytoskeleton reorganization through activation of Rho. ..
- Liverman C, Brown J, Sandhir R, Klein R, McCarson K, Berman N. Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia. Cephalalgia. 2009;29:520-31 pubmed publisher..Because the secondary allodynia in V2 after inflammation in V3 was reduced by antagonizing ERK activation in the periphery, these data suggest a peripheral component to secondary allodynia mediated through ERK activation. ..
- Wang K, Jiang Y, Chen D, Zheng J. Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways. Placenta. 2009;30:1045-51 pubmed publisher..These results also indicate that hypoxia promotes FGF2- and VEGF-stimulated cell proliferation without further activation of the PI3K/AKT1 and MEK1/2/ERK1/2, respectively. ..
- Mazurek S, Li J, Nabozny G, Reinhart G, Muthukumarana A, Harrison P, et al. Functional biomarkers of musculoskeletal syndrome (MSS) for early in vivo screening of selective MMP-13 inhibitors. J Pharmacol Toxicol Methods. 2011;64:89-96 pubmed publisher..Moreover, for targets with a mechanistic risk for MSS, the model is also conducive to inclusion in secondary pharmacodynamic studies during lead optimization to identify the best (safest) compounds for advancement into clinical trials. ..
- Hargrove J, Greenspan P, Hartle D, Dowd C. Inhibition of aromatase and ?-amylase by flavonoids and proanthocyanidins from Sorghum bicolor bran extracts. J Med Food. 2011;14:799-807 pubmed publisher..The results show that potential health benefits of sorghum bran may include actions of monomeric flavanoids as well as proanthocyanidins...
- Kakisaka K, Cazanave S, Fingas C, Guicciardi M, Bronk S, Werneburg N, et al. Mechanisms of lysophosphatidylcholine-induced hepatocyte lipoapoptosis. Am J Physiol Gastrointest Liver Physiol. 2012;302:G77-84 pubmed publisher..We concluded that LPC-induced lipoapoptosis is dependent on mechanisms largely indistinguishable from PA. These data suggest that FFA-mediated cytotoxicity is indirect via the generation of the toxic metabolite, LPC. ..
- Masyuk T, Radtke B, Stroope A, Banales J, Masyuk A, Gradilone S, et al. Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of polycystic kidney and liver disease. Gastroenterology. 2012;142:622-633.e4 pubmed publisher..Cdc25A inhibitors block cell-cycle progression and proliferation, reduce liver and kidney weights and cyst growth in animal models of polycystic kidney disease and PLD, and might be developed as therapeutics for these diseases. ..
- Ozawa M, Sakatani M, Hankowski K, Terada N, Dobbs K, Hansen P. Importance of culture conditions during the morula-to-blastocyst period on capacity of inner cell-mass cells of bovine blastocysts for establishment of self-renewing pluripotent cells. Theriogenology. 2012;78:1243-51.e1-2 pubmed publisher..In conclusion, exposure to inhibitors during the morula-blastocyst transition facilitated formation of self-renewing pluripotent cell lines from bovine blastocysts...
- García Hernández S, Potashner S, Morest D. Role of fibroblast growth factor 8 in neurite outgrowth from spiral ganglion neurons in vitro. Brain Res. 2013;1529:39-45 pubmed publisher..These findings suggest that, besides its morphogenetic role during development, FGF8 may have trophic functions in the adult which are relevant to regeneration. ..
- Xiang L, Lu S, Mittwede P, Clemmer J, Hester R. Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma. Am J Physiol Heart Circ Physiol. 2014;306:H684-9 pubmed publisher..These results suggest that obese rats are susceptible to lung injury following severe trauma due to increased production of and responsiveness to pulmonary oxidative stress. ..
- Guizzetti M, Thompson B, Kim Y, VanDeMark K, Costa L. Role of phospholipase D signaling in ethanol-induced inhibition of carbachol-stimulated DNA synthesis of 1321N1 astrocytoma cells. J Neurochem. 2004;90:646-53 pubmed..Moreover, the effect of ethanol on carbachol-induced proliferation appears to be mediated, at least in part, by its ability to interact with PLD leading to a decreased synthesis of PA. ..
- Wang Y, Ji X, Pabbidi M, Samarel A, Lipsius S. Laminin acts via focal adhesion kinase/phosphatidylinositol-3' kinase/protein kinase B to down-regulate beta1-adrenergic receptor signalling in cat atrial myocytes. J Physiol. 2009;587:541-50 pubmed publisher..These findings provide new insight into the cellular mechanisms by which the extracellular matrix can modulate atrial beta-AR signalling. ..
- Bourne C, Wakeham N, Webb N, Nammalwar B, Bunce R, Berlin K, et al. The structure and competitive substrate inhibition of dihydrofolate reductase from Enterococcus faecalis reveal restrictions to cofactor docking. Biochemistry. 2014;53:1228-38 pubmed publisher..faecalis. They also highlight a role for water in stabilizing the DHFR substrate pocket and for competitive substrate inhibitors that may gain advantages in potency by the perturbation of cofactor dynamics. ..
- Smulski D, Huang L, McCluskey M, Reeve M, Vollmer A, Van Dyk T, et al. Combined, functional genomic-biochemical approach to intermediary metabolism: interaction of acivicin, a glutamine amidotransferase inhibitor, with Escherichia coli K-12. J Bacteriol. 2001;183:3353-64 pubmed..The response to acivicin, however, was quite complex, suggesting that acivicin inhibition resonated through more than a single cellular process. ..
- Nguyen K, Hu X, Pei D. Slow-binding inhibition of peptide deformylase by cyclic peptidomimetics as revealed by a new spectrophotometric assay. Bioorg Chem. 2004;32:178-91 pubmed..This method offers several advantages over the existing PDF assays and should be particularly useful for screening PDF inhibitors in the continuous fashion. ..
- Koblish H, Hansbury M, Bowman K, Yang G, Neilan C, Haley P, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010;9:489-98 pubmed publisher..INCB024360, a potent IDO1 inhibitor with desirable pharmaceutical properties, is poised to start clinical trials in cancer patients. ..
- Liesenfeld D, Botma A, Habermann N, Toth R, Weigel C, Popanda O, et al. Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial. Cancer Epidemiol Biomarkers Prev. 2016;25:180-7 pubmed publisher..Reduction of the oncometabolite (R)-2-hydroxyglutarate identifies a novel, non-COX-inhibition-mediated mechanism of aspirin. ..
- Kim J, Kang J, Chan C. Sli15 associates with the ipl1 protein kinase to promote proper chromosome segregation in Saccharomyces cerevisiae. J Cell Biol. 1999;145:1381-94 pubmed..These genetic and biochemical studies indicate that Sli15 associates with Ipl1 to promote its function in chromosome segregation. ..
- Miao H, Wei B, Peehl D, Li Q, Alexandrou T, Schelling J, et al. Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol. 2001;3:527-30 pubmed..Our results identify EphA kinases as negative regulators of the Ras/MAPK pathway that exert anti-mitogenic functions in a cell-type-specific manner. ..
- Hebert M, Shpargel K, Ospina J, Tucker K, Matera A. Coilin methylation regulates nuclear body formation. Dev Cell. 2002;3:329-37 pubmed..Likewise, extracts prepared from cells that display gems are less efficient in methylating coilin and Sm constructs in vitro. These results demonstrate that alterations in protein methylation status can affect nuclear organization. ..
- Song K, Cornelius S, Reiss M, Danielpour D. Insulin-like growth factor-I inhibits transcriptional responses of transforming growth factor-beta by phosphatidylinositol 3-kinase/Akt-dependent suppression of the activation of Smad3 but not Smad2. J Biol Chem. 2003;278:38342-51 pubmed..In summary, our data suggest that IGF-I inhibits TGF-beta transcriptional responses through selective suppression of Smad3 activation via a PI3K/Akt-dependent pathway. ..
- Kraft A, Johnson D, Johnson J. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci. 2004;24:1101-12 pubmed..Strikingly, the change in neuronal gene expression after tBHQ treatment was dependent on Nrf2 activity in the astrocytes. This suggests that Nrf2-dependent genetic changes alter neuron-glia interactions resulting in neuroprotection. ..
- Mhawech P. 14-3-3 proteins--an update. Cell Res. 2005;15:228-36 pubmed..Gene silencing of 14-3-3sigma by CpG methylation has been found in many human cancer types. This suggests that therapy-targeting 14-3-3sigma may be beneficial for future cancer treatment. ..
- Liu M, Tarsio M, Charsky C, Kane P. Structural and functional separation of the N- and C-terminal domains of the yeast V-ATPase subunit H. J Biol Chem. 2005;280:36978-85 pubmed..The N-terminal domain alone is sufficient for activation of ATP hydrolysis in V(1), but the C-terminal domain is essential for proper communication between the V(1) and V(o) sectors. ..
- Gudz T, Komuro H, Macklin W. Glutamate stimulates oligodendrocyte progenitor migration mediated via an alphav integrin/myelin proteolipid protein complex. J Neurosci. 2006;26:2458-66 pubmed..These studies highlight novel signaling determinants of OPC migration and suggest that glutamate could play a pivotal role in regulating integrin-mediated OPC migration. ..
- Zhong S, Fields C, Su N, Pan Y, Robertson K. Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer. Oncogene. 2007;26:2621-34 pubmed..This study therefore reveals new putative NSCLC growth regulatory genes and epigenetic disease biomarkers that may enhance early detection strategies and serve as therapeutic targets. ..
- Black E, Wei J, Atluri S, Cortezzo D, Koziol Dube K, Hoover D, et al. Analysis of factors influencing the rate of germination of spores of Bacillus subtilis by very high pressure. J Appl Microbiol. 2007;102:65-76 pubmed..To elucidate the factors that determine the rate of germination of Bacillus subtilis spores with very high pressure (VHP) and the mechanism of VHP germination...
- Sullivan M, Chen H, Morikawa H. Recurrent inhibitory network among striatal cholinergic interneurons. J Neurosci. 2008;28:8682-90 pubmed publisher..This may provide a mechanism to convert activation of cholinergic interneurons into widespread recurrent inhibition of these neurons via nicotinic excitation of striatal GABAergic neurons. ..
- Zharikov S, Krotova K, Hu H, Baylis C, Johnson R, Block E, et al. Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol. 2008;295:C1183-90 pubmed publisher..We conclude that UA-induced arginase activation is a potential mechanism for reduction of NO production in PAEC. ..
- Kohr M, Traynham C, Roof S, Davis J, Ziolo M. cAMP-independent activation of protein kinase A by the peroxynitrite generator SIN-1 elicits positive inotropic effects in cardiomyocytes. J Mol Cell Cardiol. 2010;48:645-8 pubmed publisher..e., in the absence of cAMP) of PKA. Therefore, our data suggest that peroxynitrite directly activates PKA (independent from cAMP), resulting in the enhancement of myocyte contraction and relaxation through the phosphorylation of PLB. ..
- Gamarra S, Rocha E, Zhang Y, Park S, Rao R, Perlin D. Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans. Antimicrob Agents Chemother. 2010;54:1753-61 pubmed publisher..This dampening resulted in a decrease in total ergosterol levels and decreased pseudohyphal formation, a finding consistent with decreased virulence in a murine candidiasis model. ..
- Long X, Miano J. Transforming growth factor-beta1 (TGF-beta1) utilizes distinct pathways for the transcriptional activation of microRNA 143/145 in human coronary artery smooth muscle cells. J Biol Chem. 2011;286:30119-29 pubmed publisher..These results demonstrate a dual pathway for TGF-?1-induced transcription of miR143/145, thus revealing a novel mechanism underlying TGF-?1-induced human vascular SMC differentiation. ..
- Slomovitz B, Coleman R. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 2012;18:5856-64 pubmed publisher..Clinical validation of these findings is ongoing...
- Clancey L, Beirl A, Linbo T, Cooper C. Maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish. PLoS ONE. 2013;8:e65096 pubmed publisher..Taken together, these data suggest that vps11 promotes normal melanophore morphology and survival by inhibiting cathepsin release and/or activity. ..
- Hong Y, Roy R, Ambros V. Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegans. Development. 1998;125:3585-97 pubmed..In vulva precursor cells (VPCs), a pathway of heterochronic genes acts via cki-1 to maintain VPCs in G1 during the L2 stage. ..
- Peluffo R, Arguello J, Lingrel J, Berlin J. Electrogenic sodium-sodium exchange carried out by Na,K-ATPase containing the amino acid substitution Glu779Ala. J Gen Physiol. 2000;116:61-73 pubmed..M. Argüello, and J.R. Berlin. 2000. J. Gen. Physiol. 116:47-59). This model showed that alterations in the kinetics of extracellular ion-dependent reactions alone could explain the effects of Glu779Ala substitution on the Na,K-ATPase. ..
- Liu J, Kern J. Neuregulin-1 activates the JAK-STAT pathway and regulates lung epithelial cell proliferation. Am J Respir Cell Mol Biol. 2002;27:306-13 pubmed..This pathway plays an important role in NRG-1-stimulated proliferation of pulmonary epithelial cells. ..
- DiPetrillo K, Wood S, Kostrubsky V, Chatfield K, Bement J, Wrighton S, et al. Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Toxicol Appl Pharmacol. 2002;185:91-7 pubmed..The results indicate that CYP3A is responsible for the caffeine-mediated stimulation of APAP toxicity. Our results suggest that caffeine may be an additional risk factor for developing alcohol-mediated APAP hepatotoxicity. ..
- Tian G, Ghanekar S, Aharony D, Shenvi A, Jacobs R, Liu X, et al. The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors. J Biol Chem. 2003;278:28968-75 pubmed..These findings provide useful insights into the catalytic and regulatory mechanisms of gamma-secretase that may facilitate the design of novel gamma-secretase inhibitors. ..
- Knappenberger K, Tian G, Ye X, Sobotka Briner C, Ghanekar S, Greenberg B, et al. Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?. Biochemistry. 2004;43:6208-18 pubmed..It is possible that the DeltaE9 mutation causes Alzheimer's disease because cleavage activation of gamma-secretase is no longer necessary, alleviating constraints on Abeta formation. ..
- Yoo H, Kumagai A, Shevchenko A, Shevchenko A, Dunphy W. Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Cell. 2004;117:575-88 pubmed..These results indicate that the Plx1-dependent inactivation of Claspin results in termination of a DNA replication checkpoint response. ..
- Van Dross R, Yao S, Asad S, Westlake G, Mays D, Barquero L, et al. Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells. J Natl Cancer Inst. 2005;97:656-66 pubmed..The constitutive activation of K-cyclin/cdk complexes in KSHV-infected cells appears to result from the extended half-life of K-cyclin and may explain its role in Kaposi sarcoma. ..
- Yu C, Yezierski R. Activation of the ERK1/2 signaling cascade by excitotoxic spinal cord injury. Brain Res Mol Brain Res. 2005;138:244-55 pubmed..Blockade of this intracellular kinase cascade prevented the onset of injury-induced pain behavior. ..
- Li S, Fang C, Aberle N, Ren B, Ceylan Isik A, Ren J. Inhibition of PI-3 kinase/Akt/mTOR, but not calcineurin signaling, reverses insulin-like growth factor I-induced protection against glucose toxicity in cardiomyocyte contractile function. J Endocrinol. 2005;186:491-503 pubmed..Collectively, our data suggest that IGF-1 may provide cardiac protection against glucose in part through a PI-3 kinase/Akt/mTOR/ p70s6k-dependent and calcineurin-independent pathway. ..
- Schmidt L, Ballman K, Tindall D. Inhibition of fatty acid synthase activity in prostate cancer cells by dutasteride. Prostate. 2007;67:1111-20 pubmed..This is the first study to examine the effects of clinically relevant levels of dutasteride on prostate cancer cells at the molecular level and specifically, demonstrating the inhibition of FASN in these cells. ..
- Dong F, Ren J. Fidarestat improves cardiomyocyte contractile function in db/db diabetic obese mice through a histone deacetylase Sir2-dependent mechanism. J Hypertens. 2007;25:2138-47 pubmed..Collectively, these results suggest that fidarestat may protect against cardiomyocyte dysfunction in db/db mice through a Sir2-dependent pathway. ..
- Gaffield M, Betz W. Synaptic vesicle mobility in mouse motor nerve terminals with and without synapsin. J Neurosci. 2007;27:13691-700 pubmed..Thus, in TKO mice, and perhaps WT mice, a phospho-protein different from synapsin but otherwise of unknown identity is the primary regulator of synaptic vesicle mobility. ..
- Wang H, Kohr M, Traynham C, Wheeler D, Janssen P, Ziolo M. Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am J Physiol Cell Physiol. 2008;294:C1566-75 pubmed publisher..In summary, NOS1 inhibition or knockout leads to decreased contraction and slowed [Ca2+]i decline, and this effect is absent in PLB-/- myocytes. Thus NOS1 signaling modulates PLB serine16 phosphorylation, in part, via peroxynitrite. ..
- Hadden M, Hill S, Davenport J, Matts R, Blagg B. Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold. Bioorg Med Chem. 2009;17:634-40 pubmed publisher..The identification of these naphthoquinones as Hsp90 inhibitors provides a new scaffold upon which improved Hsp90 inhibitors can be developed. ..
- Parker S, Barkley R, Rino J, Vasil M. Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin. PLoS ONE. 2009;4:e4281 pubmed publisher..tuberculosis pathogenesis, identification of a novel cell wall enzyme and its inhibition has therapeutic and diagnostic implications. ..
- Qiao L, Zhang J. Inhibition of lysosomal functions reduces proteasomal activity. Neurosci Lett. 2009;456:15-9 pubmed publisher..Inhibition of lysosomal or proteasomal activities led to higher levels of chaperone heat shock cognate protein Hsc70, suggesting an attempt to compensate protein degradation deficiency by enhancing chaperone-mediated autophagy. ..
- Dailey M, Hait C, Holt P, Maguire J, Meier J, Miller M, et al. Structure-based drug design: from nucleic acid to membrane protein targets. Exp Mol Pathol. 2009;86:141-50 pubmed publisher..We also review examples of molecular modeling to understand receptors and using virtual screening against G-protein coupled receptor membrane proteins. ..
- Giannone P, Alcamo A, Schanbacher B, Nankervis C, Besner G, Bauer J. Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis. Pediatr Res. 2011;70:67-71 pubmed publisher..We speculate that PARP-1 overactivation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC. ..
- ZIMMERMAN B, Sargeant A, Landes K, Fernandez S, Chen C, Lairmore M. Efficacy of novel histone deacetylase inhibitor, AR42, in a mouse model of, human T-lymphotropic virus type 1 adult T cell lymphoma. Leuk Res. 2011;35:1491-7 pubmed publisher..Our data provide new directions for the treatment of ATL and support the further development of AR-42 against HTLV-1-associated lymphoid malignancies. ..
- Secor J, Kotha S, Gurney T, Patel R, Kefauver N, Gupta N, et al. Novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) and phospholipase D-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) attenuate mercury-induced lipid signaling lead. Int J Toxicol. 2011;30:619-38 pubmed publisher..For the first time, this study demonstrated that redox-dependent and PLD-mediated bioactive lipid signaling was involved in mercury-induced vascular EC cytotoxicity which was protected by NBMI and FIPI. ..
- Sciarretta S, Zhai P, Volpe M, Sadoshima J. Pharmacological modulation of autophagy during cardiac stress. J Cardiovasc Pharmacol. 2012;60:235-41 pubmed publisher..We will discuss the potential usefulness of different pharmacological activators and inhibitors of autophagy in the treatment of cardiac diseases. ..
- Argyros R, Nelson S, Kull A, Chen M, Stadheim T, Jiang B. A phenylalanine to serine substitution within an O-protein mannosyltransferase led to strong resistance to PMT-inhibitors in Pichia pastoris. PLoS ONE. 2013;8:e62229 pubmed publisher..Our data also indicate that the main target of these PMT-inhibitors in P. pastoris is Pmt2p, and that the F664 residue most likely interacts directly with the PMTi-compounds...
- Tsuji H, Wang W, Sunil J, Shimizu N, Yoshimura K, Uemura H, et al. Involvement of renin-angiotensin-aldosterone system in calcium oxalate crystal induced activation of NADPH oxidase and renal cell injury. World J Urol. 2016;34:89-95 pubmed publisher..Results indicate that hyperoxaluria-induced production of ROS, injury and inflammation are in part associated with the activation of Nox through renin-angiotensin-aldosterone pathway. ..
- Woodford M, Truman A, Dunn D, Jensen S, Cotran R, Bullard R, et al. Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors. Cell Rep. 2016;14:872-884 pubmed publisher..Mps1 expression level can potentially serve as a predictive indicator of tumor response to Hsp90 inhibitors. ..
- Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, et al. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19:5782-91 pubmed..The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases. ..
- Roselli C, Resko J, Stormshak F. Estrogen synthesis in fetal sheep brain: effect of maternal treatment with an aromatase inhibitor. Biol Reprod. 2003;68:370-4 pubmed..They also demonstrate that AA can be inhibited in the fetal lamb brain by treating the mother with ATD, without harming fetal development. ..
- Sylte M, Leite F, Kuckleburg C, Inzana T, Czuprynski C. Caspase activation during Haemophilus somnus lipooligosaccharide-mediated apoptosis of bovine endothelial cells. Microb Pathog. 2003;35:285-91 pubmed..These data suggest that LOS-mediated activation of caspase-3 and apoptosis of endothelial cells is caspase-8 dependent...
- Diaz Meyer N, Day C, Khatod K, Maher E, Cooper W, Reik W, et al. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J Med Genet. 2003;40:797-801 pubmed..An epimutation at KvDMR1, the absence of maternal methylation, causes the aberrant silencing of CDKN1C, some 180 kb away on the maternal chromosome. Similar to mutations at this locus, this silencing may give rise to BWS. ..
- Stanley W, Morgan E, Huang H, McElfresh T, Sterk J, Okere I, et al. Malonyl-CoA decarboxylase inhibition suppresses fatty acid oxidation and reduces lactate production during demand-induced ischemia. Am J Physiol Heart Circ Physiol. 2005;289:H2304-9 pubmed..Thus modulation of MCD activity is an effective means of regulating myocardial fatty acid oxidation under normal and ischemic conditions and reducing lactate production during demand-induced ischemia. ..
- Kessl J, Meshnick S, Trumpower B. Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi. Trends Parasitol. 2007;23:494-501 pubmed..To better understand the molecular basis of drug resistance, we have developed the yeast and bovine bc1 complexes as surrogates to model the molecular interaction of atovaquone with human and resistant pathogen enzymes. ..