Lysosomal Phospholipase A2 Activity in Pig Aqueous Humor

Abe, Akira; Hiraoka, Miki; Inatomi, Shuichiro; Ohguro, Ikuyo; Ohguro, Hiroshi

doi:10.1167/iovs.11-7891

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…9E, F). LPLA2 is a secreted protein as well as a lysosomal protein (28)(29)(30). LPLA2 activity in the CHO/LPLA2 cell-cultured medium after a 4 h treatment with or without PAzPC was three times higher than that after a 1 h treatment (data not shown).…”

Section: Degradation Of Truncated Ox-pls By Lpla2 Under Neutral Condimentioning

confidence: 92%

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2

Abe

Hiraoka

Ohguro

et al. 2017

Journal of Lipid Research

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generation and elimination of ROS affects cellular structure and function. Within lipid membranes and particles, unsaturated and polyunsaturated acyl groups conjugated at the sn-2 position of phospholipids (PLs) are susceptible to ROS inducing nonenzymatic fragmentation of the unsaturated acyl chains. As a result, various truncated oxidized glycerophospholipids (ox-PLs) are formed with an oxidized short or medium chain terminating in an aldehyde or carboxylic acid at the sn-2 position (2). The truncated ox-PLs produced under oxidative stress derive mainly from phosphatidylcholine (PC) and mediate inflammatory, apoptotic, and innate immune responses via cellular receptor-dependent or -independent pathways (3).For example, 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-snglycero-3-phosphocholine (PGPC) are found in oxidized LDL and act on intracellular signaling systems associated with platelet activating factor (PAF) receptors (4), scavenger receptors (5), and Toll-like receptors (6). Truncated ox-PLs perturb the lipid bilayer and its physical properties (7,8). Azelaoyl-PCs, including 1-palmitoyl-2-azelaoyl-snglycero-3-phosphocholine (PAzPC), can disrupt lipid membranes, inducing cytotoxicity in a receptor-independent manner (9, 10) and enhancing the interaction between Bax and mitochondrial membranes in an apoptotic pathway (11). The 1-palmitoyl-2-(9′-oxo-nonanoyl)-snglycero-3-phosphocholine (PONPC) accelerates the fibrillation of gelsolin associated with familial Finnish type Reactive oxygen species (ROS), generated enzymatically or nonenzymatically, modify proteins, nucleic acids, and lipids (1). Oxidative stress induced by an imbalance between

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Section: Degradation Of Truncated Ox-pls By Lpla2 Under Neutral Condimentioning

confidence: 92%

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2

Abe

Hiraoka

Ohguro

et al. 2017

Journal of Lipid Research

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“…Therefore, such a transacylation reaction has been used to detect the LPLA2 activity in the cell, tissue, and extracellular fl uid ( 3,6,9,10 ). In the present study, to measure the transacylase and phospholipase A2 activity of LPLA2 in the transfectants, DOPC/ sulfatide/NAS liposomes were incubated with cell extracts obtained from individual transfectants under acidic conditions.…”

Section: Immunoblottingmentioning

confidence: 96%

“…Recently, LPLA2 activity was found in the aqueous humor as well as ocular tissues in pig eye ( 10 ). The LPLA2 found in pig aqueous humor seems to be originated from ocular tissues such as the trabecular meshwork surrounding the anterior chamber and to be associated with clearance of the aqueous humor ( 10 ). These observations indicate that LPLA2 may play an important role for the host defense system in body ( 7 ) as well as for intracellular phospholipid homeostasis ( 6 ).…”

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confidence: 99%

“…Like other lysosomal enzymes, LPLA2 is secreted to extracellular space ( 8,9 ). Recently, LPLA2 activity was found in the aqueous humor as well as ocular tissues in pig eye ( 10 ). The LPLA2 found in pig aqueous humor seems to be originated from ocular tissues such as the trabecular meshwork surrounding the anterior chamber and to be associated with clearance of the aqueous humor ( 10 ).…”

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confidence: 99%

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Role of N-glycosylation of human lysosomal phospholipase A2 for the formation of catalytically active enzyme

Hiraoka

Ohguro

Abe

2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org brain is a water-soluble glycoprotein consisting of a single peptide chain with a molecular mass of 45 kDa ( 2 ). The primary structure deduced from the DNA sequences is highly preserved between mammals ( 3 ). Later, the enzyme was classifi ed as phospholipase A2, group XV ( 4 ). Lysosomal phospholipase A2 (LPLA2) has 49% of amino acid sequence identity to LCAT and belongs to the ␣ ␤ -hydrolase superfamily ( 3 ). LPLA2 is highly expressed in alveolar macrophages ( 5 ). A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, are observed in alveolar macrophages in LPLA2 Ϫ / Ϫ mice ( 6 ). In addition, older LPLA2 Ϫ / Ϫ mice present similar symptoms to human autoimmune disease ( 7 ). Like other lysosomal enzymes, LPLA2 is secreted to extracellular space ( 8, 9 ). Recently, LPLA2 activity was found in the aqueous humor as well as ocular tissues in pig eye ( 10 ). The LPLA2 found in pig aqueous humor seems to be originated from ocular tissues such as the trabecular meshwork surrounding the anterior chamber and to be associated with clearance of the aqueous humor ( 10 ). These observations indicate that LPLA2 may play an important role for the host defense system in body ( 7 ) as well as for intracellular phospholipid homeostasis ( 6 ). LPLA2 undergoes posttranslational modifi cations including a signal peptide cleavage and N -linked glycosylations ( 3 ). There are four potential N -glycosylation sites in human lysosomal phospholipase A2 (hLPLA2) More than a decade ago, we identifi ed a phospholipase A2 in MDCK cell homogenate with specifi city toward glycerophospholipids such as phosphatidylcholine and phosphatidylethanolamine under acidic conditions ( 1 ). The phospholipase is calcium-independent, localized to lysosomes, has an acidic pH optimum, and transacylates short chain ceramides. The enzyme purifi ed from bovine Manuscript received 25 June 2013 and in revised form 13 August 2013. Published, JLR Papers in Press, August 19, 2013 DOI 10.1194 Abbreviations: Ala, alanine; Asn, asparagine; hLPLA2, human lysosomal phospholipase A2; DOPC, 1,2-dioleoyl-sn -glycero-3-phosphocholine; ER, endoplasmic reticulum; LAL, lysosomal acid lipase; LPLA2, lysosomal phospholipase A2; N1A, 99-Asn to 99-Ala single mutation; N2A, 273-Asn to 273-Ala single mutation; N3A, 289-Asn to 289-Ala single mutation; N4A, 398-Asn to 398-Ala single mutation; NAS, N -acetylsphingosine; Nt, quadruple mutation (99-Asn, 273-Asn, 289-Asn, and 398-Asn replaced with alanines); PNGase F, N -glycosidase F; WT, wild-type .

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“…83 Lysosomal PLA2 has been also reported to be present in AH of humans. 110 Currently, however, only little is known about the role played by PLA2s in AH outflow and IOP despite the known critical and predominant role of this class of enzymes in producing the eicosanoids and lysophospholipids that are confirmed to modulate AH outflow and IOP. 111 Very recently, we not only confirmed the distribution pattern of 2 isoforms of calcium-independent phospholipaseA2 (iPLA2b and iPLA2g) in human TM and cultured TM cells, but also established their role in regulation of AH outflow facility.…”

Section: Raomentioning

confidence: 99%

Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

Rao

2014

Journal of Ocular Pharmacology and Therapeutics

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Homeostasis of aqueous humor (AH) outflow and intraocular pressure (IOP) is essential for normal vision. Impaired AH outflow through the trabecular meshwork (TM) and a resultant elevation in IOP are common changes in primary open-angle glaucoma (POAG), which is the most prevalent form of glaucoma. Although elevated IOP has been recognized as a definitive risk factor for POAG and lowering elevated IOP remains a mainstay for glaucoma treatment, little is known about the molecular mechanisms, especially external cues and intracellular pathways, involved in the regulation of AH outflow in both normal and glaucomatous eyes. In addition, despite the recognition that increased resistance to AH outflow via the conventional pathway consisting of TM and Schlemm's canal is the main cause for elevated IOP, there are no clinically approved drugs that target the conventional pathway to lower IOP in glaucoma patients. The aim of this article is to briefly review published work on the importance of bioactive lysophospholipids (eg, lysophosphatidic acid and sphingosine-1-phosphate), their receptors, metabolism, signaling, and role in the regulation of AH outflow via the TM and IOP, and to discuss pharmacological targeting of key proteins in the lysophospholipid signaling pathways to lower IOP in glaucoma patients.

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Lysosomal Phospholipase A2 Activity in Pig Aqueous Humor

Abstract: The present findings suggest that the phospholipase A2 activity found in pig AH under acidic conditions is due to LPLA2 and that it originates from ocular tissues surrounding the anterior chamber as well as plasma.

Cited by 10 publications

References 26 publications

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2

Role of N-glycosylation of human lysosomal phospholipase A2 for the formation of catalytically active enzyme

Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

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