ライフサイエンスコーパス: iPLA

1 Based on sequence homology, we identify IPLA-1 as the closest C. elegans homolog of human GVIA-i

2 Our studies indicate that IPLA-1 binds directly to multiple acidic phospholipids,

3 amatically elevates the specific activity of IPLA-1 in vitro.

4 on of ATP and ADP promote oligomerization of IPLA-1, which probably underlies the stimulatory effect

5 ography analyses reveal that skeletal muscle iPLA 2 exhibits properties characteristic of the iPLA 2b

6 ), and expression of multiple transcripts of iPLA 2 in skeletal muscle has been reported.

7 The truncated iPLA(2) (amino acids 514-806) generates lysophosphatidic

8 The role of caspase-3 in iPLA(2) activation and cell migration are supported by s

9 1), but not beta(4), integrin is involved in iPLA(2) activation and cell migration to laminin-10/11.

10 tify novel signaling and functional loops of iPLA(2) activation leading to migration of non-apoptotic

11 , and PCR confirmed that there was increased iPLA(2) activity and expression in neutrophils from peop

12 Moreover, increases in iPLA(2) activity and iPLA(2)beta protein expression are

13 ose increases iPLA(2)beta mRNA, protein, and iPLA(2) activity in a time-dependent manner.

14 key roles in recruiting and modulating GVIA-iPLA(2) activity in cells.

15 endent phospholipase A(2) (iPLA(2)) mRNA and iPLA(2) activity in rat myocardium.

16 Although the most potent inhibitors of GVIA iPLA(2) also inhibited GIVA cPLA(2), there were three 2-

17 g free carboxylic groups do not inhibit GVIA iPLA(2) and are, therefore, selective GIVA cPLA(2) inhib

18 ty and sequence mutations on the activity of iPLA(2) and related enzymes.

19 lipid signaling molecules, such as LPA, via iPLA(2) and/or cPLA(2) activities.

20 A phospholipase A(2) (GIVA cPLA(2)) and GVIA iPLA(2) are useful tools for defining the roles of these

21 propose the first structural model of GVIA-2 iPLA(2) as well as the interfacial lipid binding region.

22 A modified iPLA(2) assay, Western blotting, and PCR confirmed that

23 our approach is suitable for the modeling of iPLA(2) at the membrane surface.

24 vity and absent in macrophages isolated from iPLA(2) beta(-/-) mice.

25 We have developed inhibitors of GVIA iPLA(2) building upon the 2-oxoamide backbone that are u

26 iPLA(2) can be activated by caspase-3 via a proteolytic

27 the closest C. elegans homolog of human GVIA-iPLA(2) enzymes and use a combination of liposome intera

28 g RNA-mediated down-regulation of endogenous iPLA(2) expression in ovarian carcinoma HEY cells result

29 recent identification of new members of the iPLA(2) family, each inhibitable by (E)-6-(bromomethylen

30 for acidic phospholipids in regulating GVIA-iPLA(2) function.

31 D) simulations to build structural models of iPLA(2) in association with a phospholipid bilayer.

32 This study provides evidence for the role of iPLA(2) in enhanced superoxide generation in neutrophils

33 uterium exchange experiments with the GVIA-2 iPLA(2) in the presence of both phospholipid substrate a

34 se-3 inhibitor blocks cleavage of endogenous iPLA(2) induced by laminin-10/11.

35 Small interfering RNA knockdown of iPLA(2) inhibited superoxide generation by neutrophils.

36 was identified as being the most potent GVIA iPLA(2) inhibitor ever reported ( X(I)(50) 0.0000021, IC

37 nts' lymphoblasts in tissue culture with the iPLA(2) inhibitor, bromoenol lactone, partially restores

38 Another iPLA(2) inhibitor, FKGK11, also inhibited tumor developm

39 We present a novel class of GVIA iPLA(2) inhibitors based on the beta-lactone ring.

40 The development of potent GVIA iPLA(2) inhibitors is of great importance because only a

41 Hence, we propose that iPLA(2) is a potential effective and novel target for EO

42 In future studies, the proposed iPLA(2) models should provide a structural basis for und

43 l information is currently available for the iPLA(2) or its membrane complex.

44 he precise binding mode of FK ligands to the iPLA(2) should greatly improve our ability to design new

45 onsensus motif common to members of the GVIA-iPLA(2) subfamily.

46 hat is 22 000 times more active against GVIA iPLA(2) than GIVA cPLA(2).

47 Models for iPLA(2) were built by homology with the known structure

48 ively inhibiting calcium-independent PLA(2) (iPLA(2)) activity and absent in macrophages isolated fro

49 p VIA Ca(2+)-independent phospholipase A(2) (iPLA(2)) by fluoroketone (FK) ligands is examined by a c

50 Ca(2+)-independent phospholipase A(2) (GVIA iPLA(2)) has gained increasing interest recently as it h

51 trophils with the Ca(2+)-independent PLA(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) completely su

52 VI Ca(2)(+)-independent phospholipase A(2) (iPLA(2)) is a water-soluble enzyme that is active when a

53 a(2+)-independent phospholipase A(2) (GVIA-2 iPLA(2)) is composed of seven consecutive N-terminal ank

54 that calcium-independent phospholipase A(2) (iPLA(2)) is involved in epithelial ovarian cancer (EOC).

55 both calcium-independent phospholipase A(2) (iPLA(2)) mRNA and iPLA(2) activity in rat myocardium.

56 Calcium-independent phospholipase A(2) (iPLA(2)) plays a pivotal role in phospholipid remodeling

57 ular, the Group VIA phospholipase A(2) (GVIA-iPLA(2)) subfamily of enzymes functions independently of

58 of Asp(513) (a cleavage site of caspase-3 in iPLA(2)) to Ala blocks laminin-10/11-induced cleavage an

59 of a calcium-independent phospholipase A(2) (iPLA(2)), and this leads to arachidonic acid release and

60 the calcium-independent phospholipase A(2) (iPLA(2))] and AACOCF(3) [an inhibitor of both cytosolic

61 sphorylation and is diminished by inhibiting iPLA(2), cyclooxygenase, or lipoxygenase.

62 enol lactone (BEL), a selective inhibitor of iPLA(2), significantly inhibited EOC metastatic tumor gr

63 ced cleavage and activation of overexpressed iPLA(2), whereas mutation of Asp(733) to Ala has no such

64 so examined and shown to be increased via an iPLA(2)- and LOX-dependent pathway.

65 ether, our results identify a novel role for iPLA(2)-catalyzed AA release and its metabolism by 12/15

66 d activation of overexpressed and endogenous iPLA(2).

67 s that selectively and weakly inhibited GVIA iPLA(2).

68 pporting that the major target of action was iPLA(2).

69 bitor of both cytosolic PLA(2) (cPLA(2)) and iPLA(2)].

70 possibility, we find that ER stress promotes iPLA(2)beta accumulation in the mitochondria, opening of

71 from different intracellular locations, with iPLA(2)beta acting as a critical regulator of the cellul

72 pecific molecular causes and consequences of iPLA(2)beta activation are not known.

73 es or thapsigargin, that this requires prior iPLA(2)beta activation, and that p38 MAPK is involved in

74 at actions of PKC and PKA precede and follow iPLA(2)beta activation, respectively.

75 ng signaling events that occur downstream of iPLA(2)beta activation, we found that p38 MAPK is activa

76 ed by pharmacologic or genetic reductions in iPLA(2)beta activity and amplified by iPLA(2)beta overex

77 , all of which were suppressed by inhibiting iPLA(2)beta activity or expression with bromoenol lacton

78 Inhibiting iPLA(2)beta activity with bromoenol lactone or preventin

79 lial PAF production is entirely dependent on iPLA(2)beta activity.

80 DN)-treated monocytes display reduced speed, iPLA(2)beta also regulates directionality and actin poly

81 iPLA(2)beta and any associated proteins were then displa

82 amide generation, but the mechanism by which iPLA(2)beta and ceramides contribute to apoptosis is not

83 These converging observations reveal that iPLA(2)beta and cPLA(2)alpha regulate monocyte migration

84 To elucidate the association between iPLA(2)beta and ER stress, we compared beta-cell lines g

85 activated by the store-operated pathway, and iPLA(2)beta as an essential component of signal transduc

86 These data confirm the role of iPLA(2)beta as an essential mediator of endogenous SOCE

87 Immunoblotting studies indicate that iPLA(2)beta associates with mitochondria in macrophages

88 Phosphorylation of iPLA(2)beta at Tyr(616) also occurs upon induction of ER

89 i1 and a specific plasma membrane variant of iPLA(2)beta but not STIM1.

90 d to study iPLA(2)beta functions inactivates iPLA(2)beta by alkylating Cys thiols.

91 origin, our findings suggest that absence of iPLA(2)beta causes abnormalities in osteoblast function

92 These results indicate that loss of iPLA(2)beta causes age-dependent impairment of axonal me

93 ersible inactivation because oxidant-treated iPLA(2)beta contains DTT-reducible oligomers, and oligom

94 by FCL or thapsigargin but that deletion of iPLA(2)beta does not impair macrophage arachidonate inco

95 lls and suppresses increases in mSREBP-1 and iPLA(2)beta due to thapsigargin.

96 te that smooth muscle-specific expression of iPLA(2)beta exacerbates ligation-induced neointima forma

97 l migration and invasion with cells in which iPLA(2)beta expression had been down-regulated in vitro.

98 Here, we report that iPLA(2)beta expression increases in the vascular tunica

99 pancreatic islets, that this increases with iPLA(2)beta expression level, and that it is stimulated

100 nd increases toward WT levels upon restoring iPLA(2)beta expression.

101 actone (BEL) suicide substrate used to study iPLA(2)beta functions inactivates iPLA(2)beta by alkylat

102 the possibility that redox reactions affect iPLA(2)beta functions.

103 The iPLA(2)beta gene contains a sterol-regulatory element, a

104 bind to the sterol-regulatory element in the iPLA(2)beta gene to promote its transcription.

105 ree fatty acid and a 2-lysophospholipid, and iPLA(2)beta has been reported to participate in apoptosi

106 bly transfected INS-1 cells that overexpress iPLA(2)beta hydrolyze phospholipids more rapidly than co

107 Molecular knockdown of iPLA(2)beta impaired SOCE in both control cells and cell

108 ate that p38 MAPK is activated downstream of iPLA(2)beta in beta-cells incubated with insulin secreta

109 d identify a previously unrecognized role of iPLA(2)beta in bone formation.

110 first demonstration of a role for host cell iPLA(2)beta in cancer, and these findings suggest that i

111 rombin and tryptase to determine the role of iPLA(2)beta in endothelial cell membrane phospholipid hy

112 To explore the role of iPLA(2)beta in host-tumor cell interactions, we have use

113 and forskolin is amplified by overexpressing iPLA(2)beta in INS-1 cells and in mouse islets, and the

114 I-17 activation, and restoring expression of iPLA(2)beta in iPLA(2)beta-deficient cells also restores

115 negative SREBP-1 reduces basal mSREBP-1 and iPLA(2)beta in the Akita cells and suppresses increases

116 mplex relationships between Orai1, STIM1 and iPLA(2)beta in the SOCE pathway.

117 The activity of iPLA(2)beta in vitro increases upon co-incubation with c

118 occurs with time- and temperature-dependent iPLA(2)beta inactivation that is attenuated by DTT or AT

119 R chaperone calnexin, whose association with iPLA(2)beta increases upon induction of ER stress.

120 se-induced CPI-17 phosphorylation similar to iPLA(2)beta inhibition.

121 ctor-transfected cells, and is suppressed by iPLA(2)beta inhibition.

122 hosphorylation, and this is prevented by the iPLA(2)beta inhibitor bromoenol lactone.

123 kinase IIbeta, and we have characterized the iPLA(2)beta interactome further using affinity capture a

124 It has also been suggested that iPLA(2)beta is a housekeeping enzyme that regulates cell

125 a in cancer, and these findings suggest that iPLA(2)beta is a potential target for developing novel a

126 We conclude that iPLA(2)beta is an important mediator of AA release and p

127 ation, we generated transgenic mice in which iPLA(2)beta is expressed specifically in smooth muscle c

128 o investigate whether smooth muscle-specific iPLA(2)beta is involved in neointima formation, we gener

129 Upon MCP-1 stimulation, iPLA(2)beta is recruited to the membrane-enriched pseudo

130 ed iPLA(2)beta(-/-) mice to demonstrate that iPLA(2)beta is responsible for the majority of thapsigar

131 l interactions, we have used immunocompetent iPLA(2)beta knockout (iPLA(2)beta(-/-)) mice and the mou

132 >50% and were reduced further when ID8 cell iPLA(2)beta levels were lowered (by>95%) with shRNA.

133 n circulating cells, these data suggest that iPLA(2)beta may be a suitable therapeutic target for the

134 ion and neointima formation and suggest that iPLA(2)beta may represent a novel therapeutic target for

135 ess iPLA(2)beta produce biological oxidants, iPLA(2)beta might be subject to redox regulation.

136 Oxidant-treated iPLA(2)beta modifications were studied by LC-MS/MS analy

137 Recent reports indicate that iPLA(2)beta modulates mitochondrial cytochrome c release

138 rticipates in a variety of signaling events; iPLA(2)beta mRNA is expressed in bones of wild-type (WT)

139 identical to that of wild-type mice, and no iPLA(2)beta mRNA was observed in any tissue from iPLA(2)

140 We demonstrate that high glucose increases iPLA(2)beta mRNA, protein, and iPLA(2) activity in a tim

141 insulinoma cells to oxidative stress induces iPLA(2)beta oligomerization, loss of activity, and subce

142 rmation is suppressed by genetic deletion of iPLA(2)beta or by inhibiting its activity or expression

143 iPLA(2)beta or cPLA(2)alpha antisense ODN-treated adopti

144 Although iPLA(2)beta or cPLA(2)alpha antisense oligodeoxyribonucl

145 In support, inhibition of iPLA(2)beta or NSMase prevents cytochrome c release.

146 by forskolin, as well as by inactivation of iPLA(2)beta or NSMase, suggesting that iPLA(2)beta-media

147 Ca(2+)-independent phospholipase A(2) beta (iPLA(2)beta or PLA2g6A), or depletion of plasma membrane

148 but only caspase-3 cleavage is amplified in iPLA(2)beta overexpressing INS-1 cells (OE), relative to

149 ons in iPLA(2)beta activity and amplified by iPLA(2)beta overexpression.

150 These findings raise the likelihood that iPLA(2)beta participates in ER stress-induced apoptosis

151 These findings suggest that iPLA(2)beta participates in ER stress-induced macrophage

152 tic islets and insulinoma cells suggest that iPLA(2)beta participates in insulin secretion.

153 illustrate that smooth muscle cell-specific iPLA(2)beta participates in the initiation and early pro

154 of insulin secretion and apoptosis in which iPLA(2)beta participates.

155 tion and nuclear localization are blocked by iPLA(2)beta pharmacologic inhibition or genetic ablation

156 ed fatty acids, including AA, and inhibiting iPLA(2)beta prevents the muscarinic agonist-induced acce

157 ant in signaling and some cells that express iPLA(2)beta produce biological oxidants, iPLA(2)beta mig

158 Others have reported that iPLA(2)beta products activate Rho family G-proteins that

159 Moreover, increases in iPLA(2) activity and iPLA(2)beta protein expression are also observed in both

160 Expression of iPLA(2)beta protein in cultured vascular smooth muscle c

161 kinase C is involved in high glucose-induced iPLA(2)beta protein up-regulation.

162 sion level, and that it is stimulated by the iPLA(2)beta reaction product arachidonic acid.

163 selective), but not its enantiomer, (S)-BEL (iPLA(2)beta selective) or pyrrolidine (cytosolic PLA(2)a

164 Transfection of Akita cells with iPLA(2)beta small interfering RNA, however, suppresses N

165 h glucose-induced, protein kinase C-mediated iPLA(2)beta up-regulation activates the RhoA/Rho kinase/

166 tic SMCs that was dramatically attenuated in iPLA(2)beta(-/-) mice (>80% reduction at 5 min; p < 0.01

167 enesis and ascites formation were reduced in iPLA(2)beta(-/-) mice compared with wild-type (WT) mice

168 Moreover, iPLA(2)beta(-/-) mice displayed defects in SMC Ca(2+) ho

169 Accordingly, we used iPLA(2)beta(-/-) mice to demonstrate that iPLA(2)beta is

170 reduced to approximately 80% of WT levels in iPLA(2)beta(-/-) mice.

171 y approximately 5-fold) and tumorigenesis in iPLA(2)beta(-/-) mice.

172 alone rescued proliferation and migration in iPLA(2)beta(-/-) mice.

173 rescue of SMC migration and proliferation in iPLA(2)beta(-/-) mice.

174 affect Kv2.1 inactivation in beta-cells from iPLA(2)beta(-/-) mice.

175 e used immunocompetent iPLA(2)beta knockout (iPLA(2)beta(-/-)) mice and the mouse EOC cell line ID8.

176 anipulation of Group VIA phospholipase A(2) (iPLA(2)beta) activity in pancreatic islets and insulinom

177 hemotaxis, Ca(2+)-independent phospholipase (iPLA(2)beta) and cytosolic phospholipase (cPLA(2)alpha),

178 Group VIA phospholipase A(2) (iPLA(2)beta) hydrolyzes beta-cell membrane phospholipids

179 The Group VIA phospholipase A(2) (iPLA(2)beta) hydrolyzes glycerophospholipids at the sn-2

180 Group VIA phospholipase A(2) (iPLA(2)beta) in pancreatic islet beta-cells participates

181 Group VIA phospholipase A(2) (iPLA(2)beta) is expressed in phagocytes, vascular cells,

182 Whether group VIA phospholipase A(2) (iPLA(2)beta) is involved in vascular inflammation and ne

183 calcium-independent phospholipase A(2)beta (iPLA(2)beta) is required for high glucose-induced RhoA/R

184 reported that Group VIA phospholipase A(2) (iPLA(2)beta) is required for this response, but the spec

185 up VIA calcium-independent phospholipase A2 (iPLA(2)beta), were recently identified in patients with

186 kout (KO) mice lacking the group VIA PLA(2) (iPLA(2)beta), which participates in a variety of signali

187 lving Ca(2+)-independent phospholipase A(2) (iPLA(2)beta)-mediated ceramide generation, but the mecha

188 by a Ca(2+)-independent phospholipase A(2) (iPLA(2)beta)-mediated mechanism that promotes ceramide g

189 [calcium-independent phospholipase A(2)beta (iPLA(2)beta)] is important in regulating extracellular l

190 s identified 37 proteins that associate with iPLA(2)beta, and nearly half of them reside in ER or mit

191 Consistent with this, SREBP-1, iPLA(2)beta, and NSMase messages in Akita mouse islets a

192 rations of H(2)O(2), NO, and HOCl inactivate iPLA(2)beta, and this can be partially reversed by dithi

193 on the functional roles of Orai1, STIM1 and iPLA(2)beta, and will address some specific questions ab

194 Pharmacological and genetic inhibition of iPLA(2)beta, but not iPLA(2)gamma, diminishes diabetes-a

195 Regulatory proteins interact with iPLA(2)beta, including the Ca(2+)/calmodulin-dependent p

196 Interestingly, basal iPLA(2)beta, mature SREBP-1 (mSREBP-1), phosphorylated A

197 ta cells and is associated with increases in iPLA(2)beta, mSREBP-1, and NSMase in both WT and Akita c

198 lar myocytes with SERCA inhibitors activates iPLA(2)beta, resulting in hydrolysis of arachidonic acid

199 esults in augmentation of ER stress-induced, iPLA(2)beta-catalyzed hydrolysis of arachidonic acid fro

200 Collectively, our findings indicate that the iPLA(2)beta-ceramide axis plays a critical role in activ

201 , and restoring expression of iPLA(2)beta in iPLA(2)beta-deficient cells also restores high glucose-i

202 An iPLA(2)beta-FLAG fusion protein was expressed in an INS-

203 mulated lung endothelial cells isolated from iPLA(2)beta-knockout (KO) and wild type (WT) mice with t

204 red PLA(2) activity and PGI(2) production by iPLA(2)beta-KO cells were suppressed by pretreatment wit

205 release and PGI(2) production by stimulated iPLA(2)beta-KO endothelial cells were significantly redu

206 iPLA(2)beta-KO mice developed age-dependent neurological

207 We used iPLA(2)beta-KO mice generated by homologous recombinatio

208 iPLA(2)beta-KO mice will be useful for further studies o

209 on of iPLA(2)beta or NSMase, suggesting that iPLA(2)beta-mediated generation of ceramides via sphingo

210 ting and fed blood glucose concentrations of iPLA(2)beta-null and wild-type mice are essentially iden

211 aortic SMCs that was significantly slower in iPLA(2)beta-null cells (p < 0.01).

212 cytosol and that these events are blunted in iPLA(2)beta-null cells.

213 H]AA release upon FCL, this is attenuated in iPLA(2)beta-null macrophages and increases toward WT lev

214 iPLA(2)beta-null macrophages are also less sensitive to

215 beta-null mice, and here we demonstrate that iPLA(2)beta-null macrophages have reduced sensitivity to

216 WT and iPLA(2)beta-null macrophages incorporate [(3)H]arachidon

217 lycerophosphocholine lipids is unimpaired in iPLA(2)beta-null macrophages upon electrospray ionizatio

218 Furthermore, SMCs from iPLA(2)beta-null mesenteric arterial explants demonstrat

219 (2)beta mRNA was observed in any tissue from iPLA(2)beta-null mice at any age.

220 We have generated iPLA(2)beta-null mice by homologous recombination and ha

221 ly identical under normal circumstances, but iPLA(2)beta-null mice develop more severe hyperglycemia

222 ese and previous findings thus indicate that iPLA(2)beta-null mice exhibit phenotypic abnormalities i

223 Here we report that pancreatic islets from iPLA(2)beta-null mice have impaired insulin secretory re

224 ies of islets, brain, and other tissues from iPLA(2)beta-null mice is virtually identical to that of

225 o induces more severe glucose intolerance in iPLA(2)beta-null mice than in wild-type mice, but PLA(2)

226 We recently generated iPLA(2)beta-null mice, and here we demonstrate that iPLA

227 in bone mass and strength are accelerated in iPLA(2)beta-null mice.

228 he defects in migration and proliferation in iPLA(2)beta-null SMCs were restored by 2 mum AA.

229 er receptor A ligand fucoidan, and restoring iPLA(2)betaexpression with recombinant adenovirus increa

230 hat the major phospholipase in mitochondria, iPLA(2)gamma (patatin-like phospholipase domain containi

231 Moreover, Ca(2+)-induced iPLA(2)gamma activation was accompanied by the productio

232 Intriguingly, Ca(2+)-induced iPLA(2)gamma activation was completely inhibited by long

233 This study addresses the mechanisms of iPLA(2)gamma activation.

234 Complement- and EGF + ionomycin-stimulated iPLA(2)gamma activity was attenuated by the S511A/S515A

235 iPLA(2)gamma activity was monitored by quantifying prost

236 In COS-1 cells that overexpress iPLA(2)gamma and cyclooxygenase-1, PGE(2) production was

237 Collectively, these results identify iPLA(2)gamma as an important mechanistic component of th

238 Collectively, these results identify iPLA(2)gamma as an obligatory upstream enzyme that is ne

239 Mice null for iPLA(2)gamma display multiple bioenergetic dysfunctional

240 Furthermore, the iPLA(2)gamma enantioselective inhibitor (R)-(E)-6-(bromo

241 Here, we utilize iPLA(2)gamma gain of function and loss of function genet

242 ioenergetics, we generated mice null for the iPLA(2)gamma gene by eliminating the active site of the

243 serum that were also markedly attenuated by iPLA(2)gamma genetic ablation.

244 To identify the roles of iPLA(2)gamma in cellular bioenergetics, we generated mic

245 dels to demonstrate the robust activation of iPLA(2)gamma in murine myocardial mitochondria by Ca(2+)

246 hese results identify the obligatory role of iPLA(2)gamma in neuronal mitochondrial lipid metabolism

247 d with control cells, and was blocked by the iPLA(2)gamma inhibitor bromoenol lactone in both iPLA(2)

248 these results demonstrate that mitochondrial iPLA(2)gamma is activated by divalent cations and inhibi

249 We conclude that iPLA(2)gamma is essential for maintaining efficient bioe

250 Thus, complement-mediated activation of iPLA(2)gamma is mediated via ERK and p38 pathways, and p

251 In GECs, iPLA(2)gamma localized at the endoplasmic reticulum and

252 sm and membrane structure demonstrating that iPLA(2)gamma loss of function results in a mitochondrial

253 Mechanistically, genetic ablation of iPLA(2)gamma markedly decreased the calcium-stimulated p

254 us mitochondrial phospholipids in transgenic iPLA(2)gamma mitochondria revealed the robust production

255 The iPLA(2)gamma pathway is cytoprotective.

256 the mechanisms by which complement activates iPLA(2)gamma provides opportunities for development of n

257 enates from transgenic myocardium expressing iPLA(2)gamma resulted in 13- and 25-fold increases in th

258 aphthalenyl)-2H-tetrahydropyran-2-one (BEL) (iPLA(2)gamma selective), but not its enantiomer, (S)-BEL

259 emia, and insulin resistance, which occur in iPLA(2)gamma(+/+) mice after high fat feeding.

260 rometry of skeletal muscle mitochondria from iPLA(2)gamma(-/-) mice demonstrated marked decreases in

261 pocyte triglyceride content was identical in iPLA(2)gamma(-/-) mice fed either a standard diet or a h

262 Respirometry of adipocyte explants from iPLA(2)gamma(-/-) mice identified increased rates of oxi

263 terations in hippocampal lipid metabolism in iPLA(2)gamma(-/-) mice including: 1) a markedly elevated

264 In contrast, mitochondria from iPLA(2)gamma(-/-) mice were insensitive to fatty acyl-Co

265 Notably, iPLA(2)gamma(-/-) mice were lean, demonstrated abdominal

266 Liver mitochondria from iPLA(2)gamma(-/-) mice were markedly resistant to calciu

267 in comparison with hepatic mitochondria from iPLA(2)gamma(-/-) mice.

268 of these findings, cytochrome c release from iPLA(2)gamma(-/-) mitochondria was dramatically decrease

269 Moreover, mitochondria from iPLA(2)gamma(-/-) mouse liver were resistant to Ca(2+)/t

270 m underlying mitochondrial uncoupling in the iPLA(2)gamma(-/-) mouse.

271 calcium-independent phospholipase A(2)gamma (iPLA(2)gamma(-/-)) are completely resistant to high fat

272 Calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) (PNPLA8) is the predominant phospholipase

273 calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) is a critical mechanistic participant in t

274 calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) results in profound alterations in hippoca

275 calcium-independent phospholipase A(2)gamma (iPLA(2)gamma), and mitogen-activated protein kinases (MA

276 alcium-independent phospholipase A(2) gamma (iPLA(2)gamma), which possesses dual mitochondrial and pe

277 GE(2) was amplified in GECs that overexpress iPLA(2)gamma, compared with control cells, and was block

278 In GECs that overexpress iPLA(2)gamma, complement-mediated PGE(2) production was

279 d genetic inhibition of iPLA(2)beta, but not iPLA(2)gamma, diminishes diabetes-associated vascular sm

280 y, these results identify previously unknown iPLA(2)gamma-initiated signaling pathways mediated by di

281 (2)gamma inhibitor bromoenol lactone in both iPLA(2)gamma-overexpressing and control GECs.

282 e in the catalytic activity and signaling of iPLA(2)gamma.

283 ablated by (R)-BEL or by genetic ablation of iPLA(2)gamma.

284 ore calcium-independent phospholipases A(2) (iPLA(2)s) participate in the regulation of vascular tone

285 absence of acyl-CoA thioesterase activity of iPLA 2beta can lead to reduced fatty acyl-CoA generation

286 The phospholipase activity of iPLA 2beta has been demonstrated to participate in signa

287 2 exhibits properties characteristic of the iPLA 2beta isoform.

288 ns eluted from the ATP column and containing iPLA 2beta phospholipase activity also contained acyl-Co

289 Recently, purified iPLA 2beta was demonstrated to manifest a thioesterase a

290 indings therefore reveal a novel function of iPLA 2beta, related not to its phospholipase activity bu

291 ctivity in skeletal muscle preparations from iPLA 2beta-null mice is significantly reduced, relative

292 We report here that skeletal muscle from iPLA 2beta-null mice, relative to wild-type muscle, exhi

293 eneration and impair fatty acid oxidation in iPLA 2beta-null mice.

294 bromoenol lactone (BEL) suicide inhibitor of iPLA 2beta.

295 are the group VI Ca (2+)-independent PLA 2s (iPLA 2s), and expression of multiple transcripts of iPLA

296 each group), the final analysis included 88 IPLA and 87 control participants.

297 IPLA imparted no clinical benefit to children undergoing

298 The iodinated-poly(lactic acid) (iPLA) material was visualized through varying thicknesse

299 fficacy of intraperitoneal local anesthetic (IPLA) on pain after acute laparoscopic appendectomy in c

300 SUMMARY OF IPLA reduces pain in adult elective surgery.

301 We hypothesized that IPLA would improve recovery in pediatric acute laparosco