Identification of mouse and human macrophages as a site of synthesis of hepatic lipase

González-Navarro, Herminia; Zhang, Nong; Freeman, Lita A.; Bensadoun, André; Peterson, Katherine; Santamarina-Fojo, Silvia

doi:10.1016/s0022-2275(20)30107-3

Cited by 44 publications

(5 citation statements)

References 35 publications

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“…RNA purity and integrity were assessed, and first strand cDNA synthesis was performed with 2 μg of RNA using the SuperScript II reverse transcriptase kit (Invitrogen, Carlsbad, CA) according to manufacturer's instructions and then purified using the Wizard PCR Preps DNA purification system (Promega, Madison, WI). cDNA was quantified using the NanoDrop ND-1000 spectrophotometer, and 2 ng of purified cDNA was then subjected to 30 rounds of amplification using the Eppendorf Mastercycler thermal cycler using human HL RT-PCR primer sequences and conditions obtained from Gonzalez-Navarro et al (13) and normalized to GAPDH. PCR products were run on 1.5% high-resolution agarose gel and visualized under UV using the Bio-Rad Gel-Doc system using Quantity One software.…”

Section: Methodsmentioning

confidence: 99%

Hepatic High-Density Lipoprotein Secretion Regulates the Mobilization of Cell-Surface Hepatic Lipase

Chatterjee

Young²,

Pussegoda³

et al. 2009

Biochemistry

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HDL acts much like heparin to liberate hepatic lipase (HL) from cell surface proteoglycans and stimulate triglyceride clearance. Experiments were undertaken to evaluate the effects of factors that stimulate the secretion of HDL from the liver on the release of HL. Treatment of HepG2 cells with linoleic acid phospholipids (LAPL) (12 muM) promotes a similar increase in the accumulation of both HDL and HL in the cell media. LAPL also induce both apoA-I and HL release from primary human hepatocytes. Dilinoleoylphosphatidylcholine has a greater effect on both apoA-I secretion and HL release than palmitoyllinoleoylphosphatidylcholine. HL released from HepG2 cells is inactive and associated with a large HDL complex containing both apoA-I and apoA-II. Inclusion of the PPARalpha inhibitor, MK-886, or MAPK inhibitor, U0126, completely blocks the LAPL-induced apoA-I and HL accumulation in the media. LAPL-treated cell lysates, however, showed no change in HL protein expression nor HL mRNA. LAPL-induced HL release appears to be a consequence of the displacement ability of newly secreted HDL. Overexpression of pre-pro-apoA-I in HepG2 cells increased HL release, while siRNA inhibition of the apoA-I gene reduced HL in the media. The data show that factors that stimulate HDL secretion in hepatocytes act to also increase the release of HL. This may partly explain why HDL therapeutics often impact plasma triglyceride levels.

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Section: Methodsmentioning

confidence: 99%

Hepatic High-Density Lipoprotein Secretion Regulates the Mobilization of Cell-Surface Hepatic Lipase

Chatterjee

Young²,

Pussegoda³

et al. 2009

Biochemistry

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“…The DPH polarization values varied depending on the apoE isoform content of the rHDL, with the values for (E3/CE)-rHDL ( 9) < (E2/CE)rHDL ( 2 The packing order of the phospholipid headgroups also varied according to the apoE isoform content of the particles, with the TMA-DPH polarization values for spherical (E3/ CE)rHDL (9) being lower than for either the (E2/CE)rHDL (2) or the (E4/CE)rHDL (O) [p < 0.0001, (E2/CE)rHDL versus (E3/CE)rHDL and (E3/CE)rHDL versus (E4/CE)-rHDL]. This indicates that the phospholipid headgroups in (E3/CE)rHDL are less ordered than in any of the other spherical rHDL.…”

Section: Kinetics Of Hl-mediated Hydrolysis Of Triacylglycerol In (E2...mentioning

confidence: 99%

“…Hepatic lipase (HL) 1 is a 66 kDa glycoprotein that is synthesized by the liver (1) and macrophages (2). HL is also found in the ovaries and adrenals; however, there is no evidence of synthesis at these sites (3,4).…”

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confidence: 99%

Apolipoprotein E Enhances Hepatic Lipase-Mediated Hydrolysis of Reconstituted High-Density Lipoprotein Phospholipid and Triacylglycerol in an Isoform-Dependent Manner

et al. 2004

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This study compares the kinetics of hepatic lipase (HL)-mediated phospholipid and triacylglycerol hydrolysis in spherical, reconstituted high-density lipoproteins (rHDL) that contain either apolipoprotein E2 (apoE2), apoE3, apoE4, or apoA-I as the sole apolipoprotein. HL-mediated phospholipid hydrolysis was assessed by incubating various concentrations of rHDL that contained only cholesteryl esters (CE) in their core, (E2/CE)rHDL, (E3/CE)rHDL, (E4/CE)rHDL, and (A-I/CE)rHDL, with a constant amount of HL. The rate of phospholipid hydrolysis was determined as the formation of nonesterified fatty acid mass. HL-mediated triacylglycerol hydrolysis was assessed in rHDL containing CE, unlabeled triacylglycerol, and [(3)H]triacylglycerol in their core, (E2/TG)rHDL, (E3/TG)rHDL, (E4/TG)rHDL, and (A-I/TG)rHDL. Triacylglycerol hydrolysis was determined as the ratio of (3)H-labeled hydrolysis products to (3)H-labeled unhydrolyzed triacylglycerol. The rates of phospholipid hydrolysis in the (E2/CE)rHDL, (E3/CE)rHDL, and (E4/CE)rHDL were significantly greater than that in the (A-I/CE)rHDL. The rates of triacylglycerol hydrolysis were also greater in the (E2/TG)rHDL, (E3/TG)rHDL, and (E4/TG)rHDL compared to the (A-I/TG)rHDL, although to a lesser degree than observed with phospholipid hydrolysis. Furthermore, the rates of both phospholipid and triacylglycerol hydrolyses were greater in the (E2)rHDL than in either the (E3)rHDL or the (E4)rHDL. These results show that apoE increases the rate of HL-mediated phospholipid and triacylglycerol hydrolysis in rHDL and that this influence is isoform dependent.

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“…LPL is expressed by adipocytes, as well as cardiac and skeletal myocytes (4), while HL is expressed by hepatocytes (5). HL mRNA has also been detected in macrophages (6). EL is expressed by a wide range of tissues including hepatocytes, macrophages, and, uniquely within this family, endothelial cells (1,7).…”

mentioning

confidence: 99%

Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

et al. 2003

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Hepatic lipase (HL) and endothelial lipase (EL) are both members of the triglyceride lipase gene family. HL hydrolyzes phospholipids and triglycerides in triglyceride-rich lipoproteins and high-density lipoproteins (HDL). EL hydrolyzes HDL phospholipids and has low triglyceride lipase activity. The aim of this study was to determine if HL and EL hydrolyze different HDL phospholipids and whether HDL phospholipid composition regulates the interaction of EL and HL with the particle surface. Spherical, reconstituted HDL (rHDL) containing either 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC), 1-palmitoyl-2-arachidonylphosphatidylcholine (PAPC), or 1-palmitoyl-2-docosahexanoylphosphatidylcholine (PDPC) as the only phospholipid, apolipoprotein A-I as the only apolipoprotein, and either cholesteryl esters (CE) only or mixtures of CE and triolein (TO) in their core were prepared. The rHDL were similar in size and had comparable core lipid/apoA-I molar ratios. The CE-containing rHDL were used to determine the kinetics of HL- and EL-mediated phospholipid hydrolysis. For HL the V(max) of phospholipid hydrolysis for (POPC)rHDL > (PLPC)rHDL approximately (PDPC)rHDL > (PAPC)rHDL, while the K(m)(app) for (POPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (PAPC)rHDL. For EL the V(max) for (PDPC)rHDL > (PAPC)rHDL > (PLPC)rHDL approximately (POPC)rHDL, while the K(m)(app) for (PAPC)rHDL approximately (PLPC)rHDL > (POPC)rHDL > (PDPC)rHDL. The kinetics of EL- and HL-mediated TO hydrolysis was determined using rHDL that contained TO in their core. For HL the V(max) of TO hydrolysis for (PLPC)rHDL > (POPC)rHDL > (PAPC)rHDL > (PDPC)rHDL, while the K(m)(app) for (PLPC)rHDL > (POPC)rHDL approximately (PAPC)rHDL > (PDPC)rHDL. For EL the V(max) and K(m)(app) for (PAPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (POPC)rHDL. These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids.

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Identification of mouse and human macrophages as a site of synthesis of hepatic lipase

Cited by 44 publications

References 35 publications

Hepatic High-Density Lipoprotein Secretion Regulates the Mobilization of Cell-Surface Hepatic Lipase

Hepatic High-Density Lipoprotein Secretion Regulates the Mobilization of Cell-Surface Hepatic Lipase

Apolipoprotein E Enhances Hepatic Lipase-Mediated Hydrolysis of Reconstituted High-Density Lipoprotein Phospholipid and Triacylglycerol in an Isoform-Dependent Manner

Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

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