Lee R

References (8)

Title : Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis - Kim_2023_bioRxiv__
Author(s) : Kim D , Horimatsu T , Ogbi M , Goo B , Shi H , Veerapaneni P , Chouhaita R , Moses M , Prasad R , Benson TW , Harb R , Aboud G , Seller H , Haigh S , Fulton DJ , Csanyi G , Huo Y , Long X , Coffey P , Lee R , Guha A , Zeldin D , Hwang SH , Hammock BD , Weintraub NL , Kim HW
Ref : Biorxiv , : , 2023
Abstract : INTRODUCTION: Inflammation is a key pathogenic feature of abdominal aortic aneurysm (AAA). Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme that converts cytochrome P450-derived epoxides of fatty acids to the corresponding diols, and pharmacological inhibition of sEH prevented AAA formation. Both cytochrome P450 enzymes and sEH are highly expressed in the liver. Here, we investigated the role of hepatic sEH in AAA using a selective pharmacological inhibitor of sEH and hepatocyte-specific Ephx2 (which encodes sEH gene) knockout (KO) mice in two models of AAA [angiotensin II (AngII) infusion and calcium chloride (CaCl (2) ) application]. METHODS AND RESULTS: sEH expression and activity were strikingly higher in mouse liver compared with aorta and further increased the context of AAA, in conjunction with elevated expression of the transcription factor Sp1 and the epigenetic regulator Jarid1b, which have been reported to positively regulate sEH expression. Pharmacological sEH inhibition, or liver-specific sEH disruption, achieved by crossing sEH floxed mice with albumin-cre mice, prevented AAA formation in both models, concomitant with reduced expression of hepatic sEH as well as complement factor 3 (C3) and serum amyloid A (SAA), liver-derived factors linked to AAA formation. Moreover, sEH antagonism markedly reduced C3 and SAA protein accumulation in the aortic wall. Co-incubation of liver ex vivo with aneurysm-prone aorta resulted in induction of sEH in the liver, concomitant with upregulation of Sp1, Jarid1b, C3 and SAA gene expression, suggesting that the aneurysm-prone aorta secretes factors that activate sEH and downstream inflammatory signaling in the liver. Using an unbiased proteomic approach, we identified a number of dysregulated proteins [ e.g., plastin-2, galectin-3 (gal-3), cathepsin S] released by aneurysm-prone aorta as potential candidate mediators of hepatic sEH induction. CONCLUSION: We provide the first direct evidence of the liver's role in orchestrating AAA via the enzyme sEH. These findings not only provide novel insight into AAA pathogenesis, but they have potentially important implications with regard to developing effective medical therapies for AAA.
ESTHER : Kim_2023_bioRxiv__
PubMedSearch : Kim_2023_bioRxiv__
PubMedID: 37503031

Title : An integrative systems genetic analysis of mammalian lipid metabolism - Parker_2019_Nature_567_187
Author(s) : Parker BL , Calkin AC , Seldin MM , Keating MF , Tarling EJ , Yang P , Moody SC , Liu Y , Zerenturk EJ , Needham EJ , Miller ML , Clifford BL , Morand P , Watt MJ , Meex RCR , Peng KY , Lee R , Jayawardana K , Pan C , Mellett NA , Weir JM , Lazarus R , Lusis AJ , Meikle PJ , James DE , de Aguiar Vallim TQ , Drew BG
Ref : Nature , 567 :187 , 2019
Abstract : Dysregulation of lipid homeostasis is a precipitating event in the pathogenesis and progression of hepatosteatosis and metabolic syndrome. These conditions are highly prevalent in developed societies and currently have limited options for diagnostic and therapeutic intervention. Here, using a proteomic and lipidomic-wide systems genetic approach, we interrogated lipid regulatory networks in 107 genetically distinct mouse strains to reveal key insights into the control and network structure of mammalian lipid metabolism. These include the identification of plasma lipid signatures that predict pathological lipid abundance in the liver of mice and humans, defining subcellular localization and functionality of lipid-related proteins, and revealing functional protein and genetic variants that are predicted to modulate lipid abundance. Trans-omic analyses using these datasets facilitated the identification and validation of PSMD9 as a previously unknown lipid regulatory protein. Collectively, our study serves as a rich resource for probing mammalian lipid metabolism and provides opportunities for the discovery of therapeutic agents and biomarkers in the setting of hepatic lipotoxicity.
ESTHER : Parker_2019_Nature_567_187
PubMedSearch : Parker_2019_Nature_567_187
PubMedID: 30814737
Gene_locus related to this paper: human-ABHD1 , mouse-abhd1

Title : A reference genome for common bean and genome-wide analysis of dual domestications - Schmutz_2014_Nat.Genet_46_707
Author(s) : Schmutz J , McClean PE , Mamidi S , Wu GA , Cannon SB , Grimwood J , Jenkins J , Shu S , Song Q , Chavarro C , Torres-Torres M , Geffroy V , Moghaddam SM , Gao D , Abernathy B , Barry K , Blair M , Brick MA , Chovatia M , Gepts P , Goodstein DM , Gonzales M , Hellsten U , Hyten DL , Jia G , Kelly JD , Kudrna D , Lee R , Richard MM , Miklas PN , Osorno JM , Rodrigues J , Thareau V , Urrea CA , Wang M , Yu Y , Zhang M , Wing RA , Cregan PB , Rokhsar DS , Jackson SA
Ref : Nat Genet , 46 :707 , 2014
Abstract : Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.
ESTHER : Schmutz_2014_Nat.Genet_46_707
PubMedSearch : Schmutz_2014_Nat.Genet_46_707
PubMedID: 24908249
Gene_locus related to this paper: phavu-v7azs2 , phavu-v7awu7 , phavu-v7bpt6 , phavu-v7b6k3 , phavu-v7cry4

Title : Determination of LCt(50)s in anesthetized rats exposed to aerosolized nerve agents - Collins_2013_Toxicol.Mech.Methods_23_127
Author(s) : Collins JL , Peng X , Lee R , Witriol A , Pierre Z , Sciuto AM
Ref : Toxicol Mech Methods , 23 :127 , 2013
Abstract : Nerve agents pose a threat to the respiratory tract with exposure that could result in acute compromised lung performance and death. The determination of toxicity by inhalation is important for the rational development of timely therapeutic countermeasures. This study was designed to deliver aerosolized dilute nerve agents in a dose-response manner to investigate the extent of lethality of nerve agents: soman, sarin, VX and VR. Male rats (240-270 g) were anesthetized intramuscularly with 10 mg/kg xylazine and 90 mg/kg ketamine. Following anesthesia, rats were intubated with a glass endotracheal tube (ET) and placed in a glove box. The ET was connected to a closed circuit nebulizer system (Aeroneb, Aerogen, Inc.) that delivered a particle size of < 2.0 microm and was in series between the ventilator and the ET. Nerve agents were delivered by a small animal ventilator set for a volume of 2.5 mL x 60-80 breaths/min. VX or VR were nebulized and delivered in concentrations ranging from 6.25-800 microg/kg over a 10-min exposure time period. Sarin (GB) or soman (GD), 6.5-1250 microg/kg, were delivered in a similar manner. Lethality by inhalation occurred either during the 10-min exposure period or less than 15 min after the cessation of exposure. Survivors were euthanized at 24 h postexposure. LCt(50) estimates (+/- 95% confidence intervals [CIs]) were obtained from the sequential stage-wise experiments using the probit analysis. Probit analysis revealed that the LD(50) for VX was 110.7 microg/kg (CI: 73.5-166.7), VR 64.2 microg/kg (CI: 42.1-97.8); soman (GD), 167 microg/kg (CI: 90-310), and sarin (GB), 154 microg/kg (CI: 98-242), respectively. Although VR is a structural isomer of VX, the compounds appear to be markedly different in terms of toxicity when delivered by aerosol. These relationships were converted to actual 10 min LCt(50) equivalents: VX = 632.2, VR = 367, GD = 954.3 and GB = 880 mg.min/m(3). Validation of exposure was verified by the determination of blood levels of acetylcholinesterase (AChE) across doses for the agent VR.
ESTHER : Collins_2013_Toxicol.Mech.Methods_23_127
PubMedSearch : Collins_2013_Toxicol.Mech.Methods_23_127
PubMedID: 22978758

Title : Complete genome sequence of a free-living Vibrio furnissii sp. nov. strain (NCTC 11218) -
Author(s) : Lux TM , Lee R , Love J
Ref : Journal of Bacteriology , 193 :1487 , 2011
PubMedID: 21217006
Gene_locus related to this paper: vibfn-f0lr02 , vibfn-f0lug8 , vibfu-c9pbt2 , vibfu-c9pdm3 , vibfu-c9pfx8 , vibfu-c9p9p8 , vibfu-c9pl22 , vibfu-c9pet6

Title : CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance - Brown_2010_J.Lipid.Res_51_3306
Author(s) : Brown JM , Betters JL , Lord C , Ma Y , Han X , Yang K , Alger HM , Melchior J , Sawyer J , Shah R , Wilson MD , Liu X , Graham MJ , Lee R , Crooke R , Shulman GI , Xue B , Shi H , Yu L
Ref : J Lipid Res , 51 :3306 , 2010
Abstract : Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in approximately 80-95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels approximately 4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance.
ESTHER : Brown_2010_J.Lipid.Res_51_3306
PubMedSearch : Brown_2010_J.Lipid.Res_51_3306
PubMedID: 20802159
Gene_locus related to this paper: human-ABHD5 , mouse-abhd5

Title : Terrein reduces pulpal inflammation in human dental pulp cells - Lee_2008_J.Endod_34_433
Author(s) : Lee JC , Yu MK , Lee R , Lee YH , Jeon JG , Lee MH , Jhee EC , Yoo ID , Yi HK
Ref : J Endod , 34 :433 , 2008
Abstract : Terrein is a bioactive fungal metabolite whose anti-inflammatory properties are virtually unknown. The purpose of this study was to determine the effects of terrein on lipopolysaccharide (LPS)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human dental pulp cells and to determine the mechanism of the observed effects. The LPS-induced expression of ICAM-1 and VCAM-1 was inhibited by terrein in both a time- and dose-dependent manner. LPS-stimulated translocation of nuclear factor kappa B (NF-kappaB) into the nucleus, which was blocked by inhibitors of amino kinase terminal (AKT, LY294002), extracellular signal regulated kinase 1/2 (ERK 1/2, PD98059), p38 (SB203580), and c-jun NH2-terminal kinase (JNK, SP600125) or terrein. In addition, these inhibitors and terrein also reduced the level of ICAM-1 and VCAM-1 expression in LPS-induced inflammation of pulp cells. Terrein suppressed NF-kappaB activation by blocking the activation of Akt. These results strongly suggest the potential role of terrein as an anti-inflammatory modulator in pulpal inflammation.
ESTHER : Lee_2008_J.Endod_34_433
PubMedSearch : Lee_2008_J.Endod_34_433
PubMedID: 18358890
Gene_locus related to this paper: aspte-AT1

Title : The toxicity of styrene to the nasal epithelium of mice and rats: studies on the mode of action and relevance to humans - Green_2001_Chem.Biol.Interact_137_185
Author(s) : Green T , Lee R , Toghill A , Meadowcroft S , Lund V , Foster J
Ref : Chemico-Biological Interactions , 137 :185 , 2001
Abstract : Inhaled styrene is known to be toxic to the nasal olfactory epithelium of both mice and rats, although mice are markedly more sensitive. In this study, the nasal tissues of mice exposed to 40 and 160 ppm styrene 6 h/day for 3 days had a number of degenerative changes including atrophy of the olfactory mucosa and loss of normal cellular organisation. Pretreatment of mice with 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 completely prevented the development of a nasal lesion on exposure to styrene establishing that a metabolite of styrene, probably styrene oxide, is responsible for the observed nasal toxicity. Comparisons of the cytochrome P-450 mediated metabolism of styrene to its oxide, and subsequent metabolism of the oxide by epoxide hydrolases and glutathione S-transferases in nasal tissues in vitro, have provided an explanation for the increased sensitivity of the mouse to styrene. Whereas cytochrome P-450 metabolism of styrene is similar in rats and mice, the rat is able to metabolise styrene oxide at higher rates than the mouse thus rapidly detoxifying this electrophilic metabolite. Metabolism of styrene to its oxide could not be detected in human nasal tissues in vitro, but the same tissues did have epoxide hydrolase and glutathione S-transferase activities, and were able to metabolise styrene oxide efficiently, indicating that styrene is unlikely to be toxic to the human nasal epithelium.
ESTHER : Green_2001_Chem.Biol.Interact_137_185
PubMedSearch : Green_2001_Chem.Biol.Interact_137_185
PubMedID: 11551533