A Novel Intracellular Membrane-Bound Calcium-Independent Phospholipase A2

Tanaka, Haruki; Takeya, Ryu; Sumimoto, Hideki

doi:10.1006/bbrc.2000.2776

Cited by 82 publications

(78 citation statements)

References 20 publications

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“…Interestingly, unlike the constitutively active mutants of MEK1, MKK3, or MEKK1, the stimulatory effect of EGF in cells required the addition of ionomycin (to increase the cytosolic Ca 2ϩ concentration) despite the Ca 2ϩ -independent catalytic properties of iPLA 2 ␥ in vitro. In keeping with previous reports, this finding suggests that activation of iPLA 2 ␥ in agonist-stimulated cells may involve a Ca 2ϩ -regulated process (5,6), possibly activation of Ca 2ϩ -dependent protein kinases, such as calmodulin (56). Alternatively, Ca 2ϩ may enhance activation of iPLA 2 ␥ directly.…”

Section: Discussionsupporting

confidence: 90%

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Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Elimam

Papillon

Takano

et al. 2013

Journal of Biological Chemistry

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Background: Calcium-independent phospholipase A 2 ␥ (iPLA 2 ␥) is a mediator of complement-induced glomerular injury. Results: Complement stimulated iPLA 2 ␥ through activation of mitogen-activated protein kinases. Conclusion: Phosphorylation of iPLA 2 ␥ plays a role in activation and signaling. Significance: Understanding the regulation of iPLA 2 ␥ activity is essential for developing novel therapeutic approaches to glomerular injury and proteinuria.

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Section: Discussionsupporting

confidence: 90%

“…Tanaka et al (6) suggested that iPLA 2 ␥ may have multiple potential phosphorylation sites. We carried out a mutagenesis analysis of iPLA 2 ␥ to determine the regulation of iPLA 2 ␥ activity by the ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Elimam

Papillon

Takano

et al. 2013

Journal of Biological Chemistry

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“…Although iPLA 2 ␤ is principally a cytosolic enzyme, after cell activation, it can reportedly move to the nuclear or plasma membrane in a manner dependent upon protein kinase C according to the experimental system employed (19,29,30). During apoptosis, caspase-3-mediated cleavage of iPLA 2 ␤ leads to its activation (18 -21), which may be functionally associated with nuclear shrinkage in apoptotic cells (19) or to recruitment of phagocytes through the release of chemoattractant lysophosphatidylcholine from apoptotic cells (21).The second mammalian iPLA 2 isoform, group VIB iPLA 2 ␥, is homologous to iPLA 2 ␤ in the catalytic region, whereas the N-terminal regions of these two enzymes show no similarity (31,32). This suggests that the regulatory functions (and their underlying mechanisms) of iPLA 2 ␥ are distinct from those of iPLA 2 ␤.…”

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confidence: 99%

“…The second mammalian iPLA 2 isoform, group VIB iPLA 2 ␥, is homologous to iPLA 2 ␤ in the catalytic region, whereas the N-terminal regions of these two enzymes show no similarity (31,32). This suggests that the regulatory functions (and their underlying mechanisms) of iPLA 2 ␥ are distinct from those of iPLA 2 ␤.…”

mentioning

confidence: 99%

Group VIB Ca2+-independent Phospholipase A2γ Promotes Cellular Membrane Hydrolysis and Prostaglandin Production in a Manner Distinct from Other Intracellular Phospholipases A2

Murakami

Masuda

Ueda-Semmyo

et al. 2005

Journal of Biological Chemistry

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Although group VIA Ca 2؉ -independent phospholipase A 2 ␤ (iPLA 2 ␤) has been implicated in various cellular events, the functions of other iPLA 2 isozymes remain largely elusive. In this study, we examined the cellular functions of group VIB iPLA 2 ␥. Lentiviral transfection of iPLA 2 ␥ into HEK293 cells resulted in marked increases in spontaneous, stimulus-coupled, and cell deathassociated release of arachidonic acid (AA), which was converted to prostaglandin E 2 with preferred cyclooxygenase (COX)-1 coupling. Conversely, treatment of HEK293 cells with iPLA 2 ␥ small interfering RNA significantly reduced AA release, indicating the participation of endogenous iPLA 2 ␥. iPLA 2 ␥ protein appeared in multiple sizes according to cell types, and a 63-kDa form was localized mainly in peroxisomes. Electrospray ionization mass spectrometry of cellular phospholipids revealed that iPLA 2 ␥ and other intracellular PLA 2 enzymes acted on different phospholipid subclasses. Transfection of iPLA 2 ␥ into HCA-7 cells also led to increased AA release and prostaglandin E 2 synthesis via both COX-1 and COX-2, with a concomitant increase in cell growth. Immunohistochemistry of human colorectal cancer tissues showed elevated expression of iPLA 2 ␥ in adenocarcinoma cells. These results collectively suggest distinct roles for iPLA 2 ␤ and iPLA 2 ␥ in cellular homeostasis and signaling, a functional link between peroxisomal AA release and eicosanoid generation, and a potential contribution of iPLA 2 ␥ to tumorigenesis.Phospholipase A 2 (PLA 2 ) 1 catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to yield free fatty acids, including arachidonic acid (AA), and lysophospholipids. Mammalian PLA 2 enzymes have been classified into four major families, including secretory PLA 2 , cytosolic PLA 2 (cPLA 2 ), Ca 2ϩ -independent PLA 2 (iPLA 2 ), and platelet-activating factor acetyl hydrolases, each of which occurs as multiple isoforms (1, 2). Of these, the group IV cPLA 2 and group VI iPLA 2 families represent intracellular enzymes with a catalytic serine in their lipase consensus motif. Of the cPLA 2 family, cPLA 2 ␣, cPLA 2 ␤, and cPLA 2 ␦ possess a Ca 2ϩ -regulated C2 domain near the N terminus, and their function is Ca 2ϩ -dependent, whereas cPLA 2 ␥ is Ca 2ϩ -independent and membranebound (3-6). The regulatory roles for cPLA 2 ␣ in production of lipid mediators, including prostaglandins and leukotrienes, have been well documented in many studies, including gene targeting (7-10).Of the emerging iPLA 2 family, group VIA iPLA 2 ␤ has been implicated in various cellular events such as the basal fatty acid reacylation reaction (membrane remodeling) (11, 12), agonist-stimulated AA release and eicosanoid generation (13-16), cell proliferation (17), apoptosis (18 -21), exocytosis (22, 23), vascular relaxation (24), adipogenesis (25), and activation of store-operated channels and capacitative Ca 2ϩ influx (26). In iPLA 2 ␤ transgenic mice, the enzyme is activated during myocardial infarction and causes malignant ventr...

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“…Exposure of RPTC to diverse oxidants (TBHP, cumene hydroperoxide, and cisplatin) resulted in inactivation of ERiPLA 2 , an iPLA 2 similar to human Group VIB PLA 2 (6,30). Inactivation of ER-iPLA 2 occurred in the absence of cell death, indicating that decreases in activity precede cell death as opposed to being a result of cell death.…”

Section: Discussionmentioning

confidence: 98%

Inactivation of Endoplasmic Reticulum Bound Ca2+-Independent Phospholipase A2 in Renal Cells during Oxidative Stress

Cummings¹,

Gelasco

Kinsey³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. The purpose of this study was to determine the actions of oxidants on endoplasmic reticulum bound Ca 2ϩ -independent phospholipase A 2 (ER-iPLA 2 ) and phospholipids in renal cells. Exposure of renal proximal tubule cells (RPTC) to the oxidants tert-butyl hydroperoxide (TBHP), cumene hydroperoxide, and cisplatin resulted in time-and concentrationdependent decreases in the activity of ER-iPLA 2 . TBHP-induced ER-iPLA 2 inactivation was reversed by the addition of dithiothreitol to microsomes isolated from treated RPTC. TBHP also directly inactivated ER-iPLA 2 in microsomes isolated from untreated RPTC. Similar to RPTC, dithiothreitol prevented TBHP-induced ER-iPLA 2 inactivation in microsomes as did the reactive oxygen scavengers butylated hydroxytoluene and N,N'-diphenyl-p-phenylenediamine and the iron chelator deferoxamine. Electron paramagnetic resonance spin trapping demonstrated that TBHP initiated a carbon-centered radical after 1 min of exposure in microsomes, preceding ER-iPLA 2 inactivation, and further studies suggested that the formation of the carbon-centered radical species occurred after or in concert with the formation of oxygen-centered radicals. Phospholipid content was determined after TBHP exposure in the presence and absence of the ER-iPLA 2 inhibitor bromoenol lactone. Treatment of RPTC with TBHP resulted in 35% decreases in (16:0, 20:4)-phosphatidylethanolamine (PtdEtn), (18:0, 18:1)-plasmenylethanolamine (PlsEtn), a 30% decrease in (16:0, 18:3)-phosphatidylcholine (PtdCho), and a 25% decrease in (16:0, 20:4)-phosphatidylcholine (PtdCho). In contrast, treatment of RPTC with bromoenol lactone before TBHP exposure decreased the content of 11 phospholipids, decreasing a majority of PlsEtn phospholipids 60%, and 4 of the 8 PlsCho phospholipids 40%, while PtdCho and PtdEtn were marginally affected compared with TBHP. These data demonstrate that ER-iPLA 2 is inactivated by oxidants, that the mechanism of inactivation involves the oxidation of ER-iPLA 2 sulfhydryl groups, and that ER-iPLA 2 inhibition increases oxidant-induced RPTC phospholipid loss.Phospholipase A 2 (PLA 2 ) are esterases that cleave glycerophospholipids at the sn-2 position, resulting in the release of a fatty acid and a lysophospholipid (1). To date, over 19 different types of PLA 2 exist, differing in size, localization, and Ca 2ϩ requirement (2,3). Within the last 4 yr, a number of novel Ca 2ϩ -independent PLA 2 (iPLA 2 ) isoforms have been identified. Ma et al.

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A Novel Intracellular Membrane-Bound Calcium-Independent Phospholipase A2

Cited by 82 publications

References 20 publications

Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Group VIB Ca2+-independent Phospholipase A2γ Promotes Cellular Membrane Hydrolysis and Prostaglandin Production in a Manner Distinct from Other Intracellular Phospholipases A2

Inactivation of Endoplasmic Reticulum Bound Ca2+-Independent Phospholipase A2 in Renal Cells during Oxidative Stress

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