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Query: UNIPROT:P06889 (Mol)
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1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.
Clin Sci Mol Med 1976 Apr
PMID:Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue. 126 Dec 13

The effect of halothane on isoproterenol-stimulated lipolysis was determined in isolated rat epididymal fat cells. The maximal lipolytic response (Emax) activated by isoproterenol was 350 +/- 61 nmol of glycerol/10(5) cells/hr with an EC50 of 5.1 X 10(-9) M. When the adipocytes were simultaneously bubbled with 2.5% halothane, the Emax decreased to 158 +/- 43 nmol of glycerol/10(5) cells/hr and the dose response curve for isoproterenol was shifted to the right (EC50 3.5 X 10(-8) M, p less than 0.05). When lipolysis was maximally stimulated with (-)-isoproterenol (10(-6)M), the inhibitory effect of halothane was found to be both dose dependent (IC50 approximately 2.5%, v/v) and reversible following washout. Neither the nonhydrolyzable cAMP analog, 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (2 X 10(-3)M), nor forskolin (10(-6) M) was able to normalize lipolysis in the presence of halothane. The activation of cAMP-dependent protein kinase (EC 2.7.1.37) activity by isoproterenol was not different in halothane-exposed cells when compared to unexposed cells. When control adipocytes were exposed to isoproterenol (10(-6) M), there was a 2.5-fold increase in the activity of hormone-sensitive lipase (EC 3.1.1.3) from 0.64 +/- 0.13 to 1.53 +/- 0.32 pkat (pmol/sec) per mg (p less than 0.005, n = 10). However, in the presence of halothane (2.5%, v/v) isoproterenol stimulation of hormone-sensitive lipase was attenuated by 50% to values of 1.06 +/- 0.23 pkat/mg (p less than 0.01, n = 10). Halothane had no direct inhibitory effect on hormone-sensitive lipase since this enzyme's activity was unaffected when homogenates of isoproterenol-stimulated control cells were incubated with halothane. These studies suggest that halothane impairs the activation of hormone-sensitive lipase by cAMP-dependent protein kinase and in this manner inhibits beta-adrenergic-stimulated lipolysis.
Mol Pharmacol 1988 Mar
PMID:Mechanism of halothane-induced inhibition of isoproterenol-stimulated lipolysis in isolated rat adipocytes. 335 97

The phosphorylation of cytosolic and plasma membrane proteins was studied in isolated fat cells from euthyroid and thyroidectomized rats. The analysis, by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, of subcellular fractions of 32P-labelled fat cells revealed the presence of 10-12 phosphoprotein bands in the cytosol. The washed plasma membrane fraction contained 4 major phosphoproteins with estimated molecular weights of 70-67, 60, 42-40 and 26-22 kDa. Two-dimensional analysis of the 32P-labelled phosphoproteins showed that their isoelectric points were between 6.3 and 4.1. The profiles and the isoelectric points were similar in fat cells from euthyroid and thyroidectomized rats. The state of hypothyroidism did not affect the basal phosphorylation of fat cell proteins of the cytosolic or plasma membrane fractions. The incubation of fat cells from euthyroid rats in the presence of isoproterenol or dibutyryl adenosine cyclic monophosphate led to (a) an increase in the 32P labelling of cytosolic proteins which may be subunits of acetyl CoA carboxylase, ATP citrate lyase, hormone-sensitive lipase and other proteins, with apparent molecular weights between 50 and 42 kDa, and (b) an increase in the 32P labelling of plasma membrane proteins of 26-22 kDa. In the case of fat cells from hypothyroid rats, the dibutyryl adenosine cyclic monophosphate increased the 32P labelling of plasma membrane proteins, whereas in the presence of isoproterenol these reactions did not occur. These results show that thyroid hormones control the 32P labelling of proteins of the cytosol and plasma membrane fractions of rat fat cells and therefore, at least in some cases, the lipolytic and lipogenic pathways.
Mol Cell Endocrinol 1984 Dec
PMID:Thyroid hormones and fat cell phosphorylation. 609 86

To study the regulation of hormone-sensitive lipase gene in pigs, we amplified and sequenced partial porcine hormone-sensitive lipase cDNA. Nucleotide analysis indicated that porcine hormone-sensitive lipase cDNA was 86% homologous with the rat. In agreement with the rat, a 3.3 kb mRNA transcript was detected in adipose tissue but not in skeletal muscle of pigs by Northern hybridization. With more sensitive PCR method, hormone-sensitive lipase mRNA was found in adipose tissue, liver, heart, skeletal muscle, testis, and spleen. The gene expression in adipose tissue and liver was elevated after 2 days of fasting, and refeeding for another 2 days decreased the mRNA abundance. In contrast, the levels in skeletal muscle were not altered during identical nutritional transition. Combined evidences suggest that differential control may occur in porcine hormone-sensitive lipase gene in a tissue-specific fashion.
Biochem Mol Biol Int 1995 Jul
PMID:Differential responses of hormone-sensitive lipase gene to nutritional transition in adipose tissue, liver, and skeletal muscle of pigs. 754 69

Recent developments in understanding the biochemical and molecular nature of the CE hydrolases and their impact on cellular cholesterol trafficking have further defined the enzyme's mechanism of action with reasonable clarity. The availability of the cDNA probe for the human lysosomal acid lipase/CE hydrolase and the hormone-sensitive lipase now makes it possible to study CE hydrolase gene regulation and expression in human tissue; and it can now be stated with more assurance that the cytoplasmic CE hydrolase (NCEH) is most likely activated through phosphorylation by the cyclic AMP-dependent protein kinase. Evidence also shows that the NCEH is most likely identical to the hormone-sensitive lipase and that it plays an important role in cholesterol efflux properties of the cell. Recent advances in the discovery of the role of the eicosanoid/cytokine network in the regulation of CE hydrolysis, highlighted in Figure 10, further emphasize the interesting but complex nature of the cholesterol trafficking processes in cells, particularly under pathophysiological conditions such as cell injury, repair, and inflammation. It can be speculated that in several years, when the crystal structure of the CE hydrolase is known, the structure-function properties of this enzyme's catalytic domain, as it relates to the physical state of the CE substrates, should further clarify the precise role of this enzyme in intracellular cholesterol mobilization and trafficking under a variety of cellular conditions.
Adv Enzymol Relat Areas Mol Biol 1994
PMID:Regulation of cholesteryl ester hydrolases. 781 70

Many bacteria sense an appropriate growth condition or a critical population density for gene expression by producing acylhomoserine lactones (acyl-HSLs) that act as intercellular autoinduction signals. We recently showed that, in Ralstonia (Pseudomonas) solanacearum, a phytopathogenic bacterium, acyl-HSL production requires soll, which encodes a putative acyl-HSL synthase, and that its expression is positively regulated by the acyl-HSL-responsive SolR transcriptional regulator. This acyl-HSL-dependent autoinduction system is noteworthy because (i) it is regulated by a 'higher level' autoinducer system (responsive to 3-hydroxypalmitic acid methyl ester) via PhcA, a LysR-type transcriptional regulator and (ii) acyl-HSL production requires two additional unlinked loci. As reported here, cloning and sequencing of one of these other loci revealed that it encodes a homologue of RpoS, an alternative sigma factor (sigmaS) that in other bacteria activates gene expression during stationary phase or in response to stress conditions. R. solanacearum RpoS (RpoS(Rso)) was demonstrated to function as a sigma factor because when introduced in trans into an Escherichia coli rpoS mutant it largely restored expression of the RpoS-dependent bolAp1 gene. Mutation of rpoS(Rso) in R. solanacearum reduced survival during starvation and low pH conditions, but did not affect survival during exposure to hydrogen peroxide, high osmolarity or high temperature. This mutant was also altered in its production of several virulence factors and wilted tomato plants several days more slowly than the wild-type parent. Transcription of solR and soll were decreased in an rpoS(Rso) background (thereby reducing acyl-HSL production), but neither mutations in solR, soll or phcA nor addition of acyl-HSLs affected rpoS(Rso) expression. Therefore, in R. solanacearum the acyl-HSL-dependent autoinduction system is controlled both by a second autoinduction system and by the RpoS(Rso) sigma factor.
Mol Microbiol 1998 May
PMID:An RpoS (sigmaS) homologue regulates acylhomoserine lactone-dependent autoinduction in Ralstonia solanacearum. 963 52

GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating preadipocytes in response to GH. We found that the expression of both adipocyte determination and differentiation factor 1 (ADD1) and peroxisome proliferator activated receptor gamma(PPARgamma) was induced in preadipocytes during differentiation. In the presence of GH, which markedly inhibited triglyceride accumulation, no reduction in the expression level of ADD1 was observed in response to GH, whereas there was a 50% reduction in the expression of PPARgamma. The DNA binding activity of the PPARgamma/retinoid X receptor-alpha(RXRalpha) to the ARE7 element from the aP2 gene was also reduced by approximately 50% in response to GH. GH inhibited the expression of late markers of adipocyte differentiation, fatty acid synthase, aP2, and hormone-sensitive lipase by 70-80%. The antiadipogenic effect of GH was not affected by the mitogen-activated protein (MAP) kinase/ extracellular-regulated protein (ERK) kinase inhibitor PD 98059, indicating that the mitogen-activated protein kinase pathway was not involved in GH inhibition of preadipocyte differentiation. The expression of preadipocyte factor-1/fetal antigen 1 was decreased during differentiation, and GH treatment prevented this down-regulation of Pref1/FA1. A possible role for Pref-1/FA1 in mediating the antiadipogenic effect of GH was indicated by the observation that FA1 inhibited differentiation as effectively as GH. These data suggest that GH exerts its inhibitory activity in adipocyte differentiation at a step after the induction of ADD1 but before the induction of genes required for terminal differentiation.
Mol Endocrinol 1998 Aug
PMID:Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation. 971 40

The plant pathogen Erwinia chrysanthemi produces three acyl-homoserine lactones (acyl-HSLs). One has been identified as N-(3-oxohexanoyl)-homoserine lactone (OHHL), and the two others were supposed to be N (hexanoyl)-homoserine lactone (HHL) and N-(decanoyl)-homoserine lactone (DHL). The genes for a quorum-sensing signal generator (expI) and a response regulator (expR) were cloned. These genes are convergently transcribed and display high similarity to the expI-expR genes of Erwinia carotovora. ExpI is responsible for both OHHL and HHL production. Inactivation of expl had little effect on pectinase synthesis in E. chrysanthemi, as expression of only two of the pectate lyase genes, pelA and pelB, was decreased. E. chrysanthemi expR mutants still produced acyl-HSL and pectinases. However, gel shift and DNAse I footprinting experiments showed that the purified E. chrysanthemi ExpR protein binds specifically to the promoter regions of the five major pel genes. Addition of OHHL modified the ExpR-DNA bandshift profiles, indicating that ExpR interacts with OHHL and binds to DNA in different ways, depending on the OHHL concentration. Localization of the ExpR binding sites just upstream of promoter regions suggests that ExpR functions as an activator of pel expression in the presence of OHHL. The absence of a phenotype in expR mutants strongly suggests that at least an additional interchangeable ExpR homologue exists in E. chrysanthemi. Finally, transcription of expI::uidA and expR::uidA fusions is dependent on the population density, suggesting the existence of a quorum-sensing hierarchy in E. chrysanthemi. These results suggest that the expI-expR locus is part of a complex autoregulatory system that controls quorum sensing in E. chrysanthemi.
Mol Microbiol 1998 Sep
PMID:Characterization of the Erwinia chrysanthemi expI-expR locus directing the synthesis of two N-acyl-homoserine lactone signal molecules. 978 77

Many gram-negative bacteria regulate expression of specialized gene sets in response to population density. This regulatory mechanism, called autoinduction or quorum-sensing, is based on the production by the bacteria of a small, diffusible signal molecule called the autoinducer. In the most well-studied systems the autoinducers are N-acylated derivatives of L-homoserine lactone (acyl-HSL). Signal specificity is conferred by the length, and the nature of the substitution at C-3, of the acyl side-chain. We evaluated four acyl-HSL bioreporters, based on tra of Agrobacterium tumefaciens, lux of Vibrio fischeri, las of Pseudomonas aeruginosa, and pigment production by Chromobacterium violaceum, for their ability to detect sets of 3-oxo acyl-HSLs, 3-hydroxy acyl-HSLs, and alkanoyl-HSLs with chain lengths ranging from C4 to C12. The traG::lacZ fusion reporter from the A. tumefaciens Ti plasmid was the single most sensitive and versatile detector of the four. Using this reporter, we screened 106 isolates representing seven genera of bacteria that associate with plants. Most of the Agrobacterium, Rhizobium, and Pantoea isolates and about half of the Erwinia and Pseudomonas isolates gave positive reactions. Only a few isolates of Xanthomonas produced a detectable signal. We characterized the acyl-HSLs produced by a subset of the isolates by thin-layer chromatography. Among the pseudomonads and erwinias, most produced a single dominant activity chromatographing with the properties of N-(3-oxo-hexanoyl)-L-HSL. However, a few of the erwinias, and the P. fluorescens and Ralstonia solanacearum isolates, produced quite different signals, including 3-hydroxy forms, as well as active compounds that chromatographed with properties unlike any of our standards. The few positive xanthomonas, and almost all of the agrobacteria, produced small amounts of a compound with the chromatographic properties of N-(3-oxo-octanoyl)-L-HSL. Members of the genus Rhizobium showed the greatest diversity, with some producing as few as one and others producing as many as seven detectable signals. Several isolates produced extremely nonpolar compounds indicative of very long acyl side-chains. Production of these compounds suggests that quorum-sensing is common as a gene regulatory mechanism among gram-negative plant-associated bacteria.
Mol Plant Microbe Interact 1998 Nov
PMID:Production of acyl-homoserine lactone quorum-sensing signals by gram-negative plant-associated bacteria. 980 99

Lipotransin is a novel hormone-sensitive lipase (HSL)-interacting protein that appears to translocate HSL to the lipid droplet. The interaction of the two proteins depends upon the phosphorylation of HSL by protein kinase A. Once formed, the complex is dissociated by ATP hydrolysis, due to the ATPase activity of lipotransin. In 3T3L1 adipocytes, insulin produces a stable complex between the proteins, due to a modification of lipotransin. Thus, lipotransin is a novel docking protein that may direct the hormonally regulated redistribution of hormone-sensitive lipase.
Mol Cell 1999 Jul
PMID:Lipotransin: a novel docking protein for hormone-sensitive lipase. 1044 32


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