Mechanisms involved in the synthesis of disaturated phosphatidylcholine by alveolar type ii cells isolated from adult rat lung

Post, Martin; Schuurmans, E. A. J. M.; Batenburg, Joseph J.; Golde, L.M.G. Van

doi:10.1016/0005-2760(83)90205-9

Cited by 75 publications

(26 citation statements)

References 39 publications

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“…Formation of SatPC by the remodeling pathway occurs in 2 concerted reactions: deacylation of monosaturated PC by a phospholipase A 2 (PLA 2 ), followed by reacylation of the resultant 1-palmitoyl-2-lysophosphatidylcholine with palmitoyl-CoA by a lysophosphatidylcholine (lysoPC) acyltransferase. While the importance of the remodeling pathway to SatPC production has been known for many years (14)(15)(16)(17), little is known regarding the regulation of this pathway, largely due to an inability to clone the enzymes involved.…”

Section: Introductionmentioning

confidence: 99%

LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice

Bridges¹,

Ikegami²,

Brilli³

et al. 2010

J. Clin. Invest.

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Respiratory distress syndrome (RDS), which is the leading cause of death in premature infants, is caused by surfactant deficiency. The most critical and abundant phospholipid in pulmonary surfactant is saturated phosphatidylcholine (SatPC), which is synthesized in alveolar type II cells de novo or by the deacylation-reacylation of existing phosphatidylcholine species. We recently cloned and partially characterized a mouse enzyme with characteristics of a lung lysophosphatidylcholine acyltransferase (LPCAT1) that we predicted would be involved in surfactant synthesis. Here, we describe our studies investigating whether LPCAT1 is required for pulmonary surfactant homeostasis. To address this issue, we generated mice bearing a hypomorphic allele of Lpcat1 (referred to herein as Lpcat1 GT/GT mice) ufsing a genetrap strategy. Newborn Lpcat1 GT/GT mice showed varying perinatal mortality from respiratory failure, with affected animals demonstrating hallmarks of respiratory distress such as atelectasis and hyaline membranes. Lpcat1 mRNA levels were reduced in newborn Lpcat1 GT/GT mice and directly correlated with SatPC content, LPCAT1 activity, and survival. Surfactant isolated from dead Lpcat1 GT/GT mice failed to reduce minimum surface tension to wild-type levels. Collectively, these data demonstrate that full LPCAT1 activity is required to achieve the levels of SatPC essential for the transition to air breathing.

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Section: Introductionmentioning

confidence: 99%

LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice

Bridges¹,

Ikegami²,

Brilli³

et al. 2010

J. Clin. Invest.

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“…Formation of DPPC by the remodeling mechanism involves deacylation of unsaturated PC at the sn-2 position by a phospholipase A2, followed by reacylation of the resultant 1-palmitoyl-2-lysophosphatidylcholine with palmitoyl-CoA via a lysophosphatidylcholine (lysoPC) acyltransferase. Because of the preferential incorporation of radiolabeled palmitate into the sn-2 position of surfactant DPPC by type II cells and lung microsomes, PC remodeling has been recognized as a major pathway for DPPC synthesis for many years (1)(2)(3). It is estimated that 55-75% of the DPPC found in type II cells is formed by this remodeling pathway (4,5).…”

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confidence: 99%

Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells

Chen

Hyatt

Mucenski

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

176

187

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Pulmonary surfactant is a complex of lipids and proteins produced and secreted by alveolar type II cells that provides the low surface tension at the air-liquid interface. The phospholipid most responsible for providing the low surface tension in the lung is dipalmitoylphosphatidylcholine. Dipalmitoylphosphatidylcholine is synthesized in large part by phosphatidylcholine (PC) remodeling, and a lysophosphatidylcholine (lysoPC) acyltransferase is thought to play a critical role in its synthesis. However, this acyltransferase has not yet been identified. We have cloned full-length rat and mouse cDNAs coding for a lysoPC acyltransferase (LPCAT). LPCAT encodes a 535-aa protein of Ϸ59 kDa that contains a transmembrane domain and a putative acyltransferase domain. When transfected into COS-7 cells and HEK293 cells, LPCAT significantly increased lysoPC acyltransferase activity. LPCAT preferred lysoPC as a substrate over lysoPA, lysoPI, lysoPS, lysoPE, or lysoPG and prefers palmitoyl-CoA to oleoyl-CoA as the acyl donor. This LPCAT was preferentially expressed in the lung, specifically within alveolar type II cells. Expression in the fetal lung and in rat type II cells correlated with the expression of the surfactant proteins. LPCAT expression in fetal lung explants was sensitive to dexamethasone and FGFs. KGF was a potent stimulator of LPCAT expression in cultured adult type II cells. We hypothesize that LPCAT plays a critical role in regulating surfactant phospholipid biosynthesis and suggest that understanding the regulation of LPCAT will offer important insight into surfactant phospholipid biosynthesis.biochemistry ͉ lung ͉ surfactant ͉ phosphatidylcholine

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“…On the one hand, dipalmitoyl-PtdEtn was not formed from endogenous diacylglycerol (Post et al, 1983, Riistow & Kunze, 1984. Labelled glycerol, on the other hand, was incorporated into dipalmitoyl-PtdEtn.…”

Section: Discussionmentioning

confidence: 99%

“…In order to explain the high content of dipalmitoyl-PtdCho, three different mechanisms have been suggested: (i) synthesis de novo (Crecelius & Longmore, 1984b); (ii) reacylation of lyso-PtdCho with palmitoyl-CoA by the forward reaction of the acyl-CoA:lysoPtdCho acyltransferase (Mason & Dobbs, 1980;Post et al, 1983); and (iii) acyl exchange between unsaturated fatty acid in the sn-2 position of PtdCho and palmitoyl-CoA, involving the reverse reaction of the acyltransferase, as shown in lung microsomes (Stymne & Stobert, 1985), and possibly also indirectly by transacylation of unsaturated fatty acids from PtdCho to lysoPtdEtn (Nijssen & Van den Bosch, 1986b). In contrast with the surfactant lipids PtdCho, PtdGro and Ptdlns (Goerke, 1974;Hallman et al, 1985;Schlame et al, 1986;Rustow et al, 1988), surfactant PtdEtn contained only trace amounts of dipalmitoyl species.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast with the surfactant lipids PtdCho, PtdGro and Ptdlns (Goerke, 1974;Hallman et al, 1985;Schlame et al, 1986;Rustow et al, 1988), surfactant PtdEtn contained only trace amounts of dipalmitoyl species. Thus it appears that endogenous dipalmitoylglycerol of lung microsomes (Rustow & Kunze, 1984) and of type II cells (Post et al, 1983) is hardly used to synthesize dipalmitoylPtdEtn. It has to be taken into account, however, that both endogenous diacylglycerols and those formed de novo represent different substrate pools for the biosynthesis of PtdCho and PtdEtn (Binaglia et al, 1982;Rustow & Kunze, 1985.…”

Section: Introductionmentioning

confidence: 99%

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Studies on the formation of dipalmitoyl species of phosphatidylcholine and phosphatidylethanolamine in pulmonary type II cells

Rüstow

Schlame

Haupt

et al. 1992

Biochemical Journal

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Endogenous content of and incorporation of labelled glycerol into alkenylacyl-, alkylacyl-and diacyl-glycerol, -glycero-3-phosphocholine and -glycero-3-phosphoethanolamine of pulmonary type II cells were measured. On prolonged incubation of type II cells with labelled glycerol, the proportion of label incorporated into the diacyl subclass of these glycerolipids increased and the proportion of label incorporated into the ether lipids declined. Endogenous phosphatidylcholine (PtdCho) of type II cells contained 38.40 of the dipalmitoyl species, but endogenous phosphatidylethanolamine (PtdEtn) only 2.5 %. In contrast, similar proportions of labelled glycerol were incorporated into dipalmitoyl-PtdCho and -PtdEtn after short-time incubation but, with prolonged incubation time the proportion of labelled dipalmitoyl-PtdCho increased from 11.3 to 18.8 %, whereas that of dipalmitoyl-PtdEtn did not change significantly. Type II cell membranes were found to exhibit cofactor-independent and CoA-mediated transacylations of [1_-4C]palmitoyl-lyso-PtdCho and -lyso-PtdEtn. The distribution of label among the palmitic acid-containing species of PtdCho and PtdEtn formed by both transacylation activities was determined. Cofactor-independent and CoA-mediated transacylation showed a strong selectivity for palmitate and arachidonate and a strong discrimination against oleate. The amount (nmol) of dipalmitoyl-PtdEtn formed by both transcylation activities after short-time incubation (2 min) decreased with prolonged incubation time (60 min). In contrast, the nmol of dipalmitoyl-PtdCho formed by cofactorindependent transacylation remains nearly the same after short-time and longer incubation. The nmol of dipalmitoylPtdCho formed by CoA-mediated transacylation increased strongly in the same time interval. Beside synthesis de novo via the CDP-choline pathway and reacylation of lyso-PtdCho with palmitoyl-CoA, the CoA-mediated transacylation of lyso-PtdCho may be an effective pathway for the formation of dipalmitoyl-PtdCho in pulmonary type II cells.

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Mechanisms involved in the synthesis of disaturated phosphatidylcholine by alveolar type ii cells isolated from adult rat lung

Cited by 75 publications

References 39 publications

LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice

LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice

Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells

Studies on the formation of dipalmitoyl species of phosphatidylcholine and phosphatidylethanolamine in pulmonary type II cells

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