Generation of phosphatidic acid during calcium‐loading of human erythrocytes

Bütikofer, Peter; Yee, Maggie C.; Schott, Mary Ann; Lubin, Bertram H.; Kuypers, Frans A.

doi:10.1111/j.1432-1033.1993.tb17770.x

Cited by 19 publications

(19 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Permeabilization and increase in cytosolic calcium will trigger many pathways, including those that lead to a loss in phospholipid asymmetry and the activation of phospholipases including phospholipase D (27). Under such conditions, it is difficult to determine the direct effect of calcium on the LPCAT enzyme in the RBC membranes.…”

Section: Discussionmentioning

confidence: 99%

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Soupène¹,

Fyrst²,

Kuypers³

2008

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

Self Cite

107

View full text Add to dashboard Cite

The mammalian RBC lacks de novo lipid synthesis but maintains its membrane composition by rapid turnover of acyl moieties at the sn-2 position of phospholipids. Plasma-derived fatty acids are esterified to acyl-CoA by acyl-CoA synthetases and transferred to lysophospholipids by acyl-CoA:lysophospholipid acyltransferases. We report the characterization of three lysophosphatidylcholine (lysoPC) acyltransferases (LPCATs), products of the AYTL1, -2, and -3 genes. These proteins are three members of a LPCAT family, of which all three genes are expressed in an erythroleukemic cell line. Aytl2 mRNA was detected in mouse reticulocytes, and the presence of the product of the human ortholog was confirmed in adult human RBCs. The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes. Spliced variants of Aytl1, affecting a conserved catalytic motif, were identified. Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus. Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein.phosphatidylcholine ͉ RBC ͉ AYTL2

show abstract

Section: Discussionmentioning

confidence: 99%

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Soupène¹,

Fyrst²,

Kuypers³

2008

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

Self Cite

107

View full text Add to dashboard Cite

show abstract

“…Generation of phosphatidic acid by phospholipase D does not contribute to the 4␤PMA response PA is readily generated not only from DAG via DGK, but also from cleavage of phosphatidylcholine by the action of the PKCactivated enzyme phospholipase D (PLD) (Butikofer et al, 1993;Bollag et al, 2005). We therefore asked whether blocking the action of PLD by 1-butanol could occlude the 4␤PMA facilitation, which would indicate a role for this mechanism of PA synthesis in the phorbol response.…”

Section: Is Activated Dgk the Final Arbiter That Controls Hcn Channelmentioning

confidence: 99%

HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2

Fogle¹,

Lyashchenko²,

Turbendian³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…LPA Formation-Conditions that lead to PS exposure are associated with activation of phospholipase D (12). When cells are incubated under conditions that increase their intracellular calcium, phosphatidylcholine is hydrolyzed and PA is formed (12).…”

Section: Hydrolysis Of Normal and Ps-exposing Red Blood Cells By Splamentioning

confidence: 99%

“…We have reported that under conditions that lead to PS exposure in red blood cells, an intracellular phospholipase D is activated that generates phosphatidic acid (PA) by hydrolysis of phosphatidylcholine (12). We hypothesized that the interaction between sPLA 2 and PS-exposing red blood cells could result in lysophosphatidic acid (LPA) generation from PA present at elevated levels in these cells.…”

mentioning

confidence: 99%

Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Neidlinger

Larkin²,

Bhagat³

et al. 2006

Journal of Biological Chemistry

Self Cite

103

View full text Add to dashboard Cite

Secretory phospholipase A 2 (sPLA 2 ) type IIa, elevated in inflammation, breaks down membrane phospholipids and generates arachidonic acid. We hypothesized that sPLA 2 will hydrolyze red blood cells that expose phosphatidylserine (PS) and generate lysophosphatidic acid (LPA) from phosphatidic acid that is elevated in PS-exposing red blood cells. In turn, LPA, a powerful lipid mediator, could affect vascular endothelial cell function. Although normal red blood cells were not affected by sPLA 2 , at levels of sPLA 2 observed under inflammatory conditions (100 ng/ml) PS-exposing red blood cells hemolyzed and generated LPA (1.2 nM/10 8 RBC). When endothelial cell monolayers were incubated in vitro with LPA, a loss of confluence was noted. Moreover, a dose-dependent increase in hydraulic conductivity was identified in rat mesenteric venules in vivo with 5 M LPA, and the combination of PS-exposing red blood cells with PLA 2 caused a similar increase in permeability. In the presence of N-palmitoyl L-serine phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss of confluence in vitro and the hydraulic permeability caused by 5 M LPA in vivo were abolished. The present study demonstrates that increased sPLA 2 activity in inflammation in the presence of cells that have lost their membrane phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss of vascular integrity.Secretory phospholipase A 2 (sPLA 2 ) 2 type IIa is a low molecular weight, ubiquitous enzyme that is elevated in inflammation. The enzyme generates arachidonic acid from phospholipids for the generation of thromboxanes and leukotrienes and, as such, acts as an essential mediator in the inflammatory pathways (1). The specific membranes targeted by the enzyme for the generation of arachidonic acid during inflammation have not been clearly defined. Secretory PLA 2 has a strong preference for phospholipids that are negatively charged at physiologic pH: phosphatidylserine (PS) and phosphatidylethanolamine (PE) (2). In normal mammalian cells, these phospholipids are mainly (PE) or exclusively (PS) confined to the inner layer of the plasma membrane (1-3). Loss of this asymmetric distribution and exposure of PS on the external surface generates a thrombogenic surface and signals macrophages to remove cells by phagocytosis (1-5). Although normal mammalian cells do not seem to act as targets for sPLA 2 , loss of phospholipid asymmetry in plasma membranes and the exposure of PS have been shown to render them vulnerable to phospholipid hydrolysis (1). In addition, it has been well established that bacterial membranes are excellent substrates for this enzyme (6). Together, membranes with altered phospholipid packing are potential targets for sPLA 2 type IIa.We have previously shown that sPLA 2 is elevated after injury, predicts hypoxemia, and is related to multiorgan failure (7,8). In addition, elevated levels of sPLA 2 predict the onset of the acute chest syndrome in sickle cell disease (9 -11), the severe lung damage that...

show abstract

Generation of phosphatidic acid during calcium‐loading of human erythrocytes

Cited by 19 publications

References 50 publications

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2

Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Contact Info

Product

Resources

About