Disease relevance of Cel

• Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester [1].
• Liposomes composed of chemically synthesized glyceroglycolipids, such as 1,2-dipalmityl-[beta-cellobiosyl-(1'----3)]- glycerol (Cel-DAG), 1,2-dipalmityl-[beta-lactosyl-(1'----3)]-glycerol, or 1,2-dipalmityl-[beta-maltosyl-(1'----3)]-glycerol, were found to enhance protective immunity against transplantable tumor cells (sarcoma 180) in ICR mice [2].
• Tissue inflammation, goblet cell hyperplasia, and IL-4, IL-5, and IL-13 levels in BAL fluid were significantly reduced in fB-/- mice compared with C4-/- and WT mice [3].
• Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge [4].
• However, different injury mechanisms were operative since (1) CE, but not CO, toxicity significantly altered cell phospholipid profiles, and (2) 2 mmol/L glycine completely blocked CE- but not CO-mediated cell death [5].

High impact information on Cel

• Neutral cholesterol esterase, diglyceride lipase, and monoglyceride lipase were also activated (117%, 10%, and 37+, respectively) by cyclic AMP-dependent protein kinase [6].
• BAL 31 deletions revealed that sequences up to 20 bp upstream of the major transcription start site could be removed without any significant loss of CAT activity [7].
• Carboxyl ester lipase expression in macrophages increases cholesteryl ester accumulation and promotes atherosclerosis [8].
• Carboxyl ester lipase (CEL, also called cholesterol esterase or bile salt-dependent lipase) is a lipolytic enzyme capable of hydrolyzing cholesteryl esters, triacylglycerols, and phospholipids in a trihydroxy bile salt-dependent manner but hydrolyzes ceramides and lysophospholipids via bile salt-independent mechanisms [8].
• Although the absolute numbers of eosinophils in BAL fluids were similar between the strains, very few CD8(+) T cells could be detected in lungs of IFN-alphabetagammaR(-/-) animals, leaving eosinophils as the predominant leukocyte [9].

Chemical compound and disease context of Cel

• To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA [1].
• Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles [10].
• RESULTS: The 10-day animals developed allergic airway disease, characterized by BAL eosinophilia, histologic airway inflammation and mucus secretion, methacholine hyperresponsiveness, and OVA-specific IgE production [11].
• Amelioration by BAL (2,3-dimercapto-1-propanol) and DMPS (sodium 2,3-dimercapto-1-propanesulfonic acid) of arsenite developmental toxicity in mice [12].
• Amelioration by BAL and DMPS of arsenite developmental toxicity was assessed at 15, 30, and 60 mg/kg/day, and 75, 150, and 300 mg/kg/day, respectively [12].

Biological context of Cel

• In this paper we have analysed the endogenous CEL gene expression in mammary gland [13].
• The carboxyl ester lipase gene resides on chromosome 2 [14].
• Hence we have demonstrated that the prolactin/STAT5 signal is not involved in a general and significant activation of 'milk genes'. Instead of a direct effect of the lactogenic hormones, the up-regulation of the CEL gene is correlated with an increase in the number of differentiated epithelial cells [13].
• Inhibition of carboxyl ester lipase activity in HepG2 cells reduced hydrolysis of high density lipoprotein-cholesteryl esters approximately 40% [15].
• These results indicate that cholesterol esterase is responsible for mediating intestinal absorption of cholesteryl esters but does not play a primary role in free cholesterol absorption [16].

Anatomical context of Cel

• Studies of the regulation of the mouse carboxyl ester lipase gene in mammary gland [13].
• Furthermore, promoter studies using the mammary-gland-derived cell line, HC11, show that a major positive element in the CEL gene promoter interacts with a member(s) of the CCAAT-binding transcription factor/nuclear factor 1 family, binding to a palindromic site [13].
• The recombinant BSSL produced was purified, biochemically characterized and compared to native BSSL and recombinant BSSL produced in mouse C127 and hamster CHO cells [17].
• The ratio of the two radiolabels excreted in the feces over a 24-h period was found to be similar in the control and cholesterol esterase-null mice [16].
• Carboxyl ester lipase cofractionates with scavenger receptor BI in hepatocyte lipid rafts and enhances selective uptake and hydrolysis of cholesteryl esters from HDL3 [15].

Associations of Cel with chemical compounds

• Additions of cAMP and ATP resulted in 40-70% activation of both triglyceride lipase and cholesterol esterase [18].
• Serum cholesterol levels were not significantly different between control and cholesterol esterase-null mice fed either control or an atherogenic diet [16].
• In contrast to these results, when experiments were performed with [3H]cholesteryl oleate instead of [3H]cholesterol, a higher amount of the 3H radiolabel was found excreted in feces and dramatically less of the radiolabel was detected in the serum of the cholesterol esterase-null mice in comparison with that detected in control animals [16].
• Previous work showed that carboxyl ester lipase enhanced selective uptake of cholesteryl ether from high density lipoprotein by an unknown mechanism [15].
• Heparin blockage of cell-surface proteoglycans also prevented carboxyl ester lipase stimulation of cholesteryl ester uptake by HepG2 cells [15].

Regulatory relationships of Cel

• Cholesterol absorption results were similar between the control and cholesterol esterase-null mice regardless of whether the animals were fed a low fat diet or a high fat/high cholesterol diet [16].

Other interactions of Cel

• Even though the CEL and WAP genes are induced at the same time during mammary gland differentiation, their regulation is different with respect to dependence on lactogenic hormones [13].
• Since lipoprotein lipase has no activity toward cholesteryl oleate, activation of cholesterol esterase in untreated S1 was readily demonstrable [18].
• When added to cultures of HepG2 cells, carboxyl ester lipase cofractionated with scavenger receptor BI and [(3)H]cholesteryl ether-labeled high density lipoprotein in lipid raft fractions of cell homogenates [15].
• Activation of myocardial neutral triglyceride lipase and neutral cholesterol esterase by cAMP-dependent protein kinase [18].
• The tissue-specific regulation of the carboxyl ester lipase gene in exocrine pancreas differs significantly between mouse and human [19].

Analytical, diagnostic and therapeutic context of Cel

• Recombinant BSSL derived from transgenic mice showed a different migration and distribution after SDS-PAGE electrophoresis, lower apparent molecular mass on size-exclusion chromatography and no detectable interactions with a panel of lectins [17].
• Confocal microscopy of immunostained carboxyl ester lipase and scavenger receptor BI showed a close association of these proteins in HepG2 cells [15].
• Cytology, immunocytochemistry, cytokine and immunoglobulin measurements, and cell type accumulation in lung, BAL fluid, plasma, and hemopoietic tissues were carried out [20].
• Molecular cloning and characterization of the mouse carboxyl ester lipase gene and evidence for expression in the lactating mammary gland [21].
• We have also analyzed expression of the CEL gene in the mammary glands from other species by performing a Northern blot analysis with RNA from goat and cow [21].

References