ライフサイエンスコーパス: iPLA(2)

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

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

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

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

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

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

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

8 iPLA2 localized to mitochondria even before apoptotic in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

31 ng a calcium-independent phospholipase A(2), iPLA2-VIA, which also prevents cardiolipin depletion/mon

32 calcium-independent phospholipase A2 (Ca(2+)-iPLA2) activity by MJ33 on fertilization competence of m

33 MJ33 inhibited the PRDX6 Ca(2+)-iPLA2 activity and reduced these parameters in WT sperma

34 nclusion, the inhibition of the PRDX6 Ca(2+)-iPLA2 activity promotes an oxidative stress affecting vi

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

36 F) and calcium-independent phospholipase A2 (iPLA2) in activation of Ca2+ release-activated Ca2+ (CRA

37 6a and calcium-independent phospholipase A2 (iPLA2) in Golgi enzyme recycling, and show that retrogra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

53 and the calcium-independent PLA2s (cPLA2 and iPLA2), are key enzymes mediating oligomeric amyloid-bet

54 genous iPLA2 transcription in both INS-1 and iPLA2-expressing INS-1 cells without affecting the expre

55 e major intracellular PLA2s, cPLA2alpha, and iPLA2, generate arachidonic acid and lysophosphatic acid

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

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

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

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

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

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

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

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

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

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

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

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

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

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

70 amma-KO mice showed no alteration in cardiac iPLA2 activity and produced less PGE2.

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

72 >50% and were reduced further when ID8 cell iPLA(2)beta levels were lowered (by>95%) with shRNA.

73 icantly advance our understanding of the CIF-iPLA2-dependent mechanism of activation of ICRAC and sto

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

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

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

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

78 we found that STS down-regulated endogenous iPLA2 transcription in both INS-1 and iPLA2-expressing I

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

104 the Drosophila homologue of the PLA2G6 gene, iPLA2-VIA, results in reduced survival, locomotor defici

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

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

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

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

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

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

111 man Group VIA calcium-independent PLA2 (GVIA iPLA2).

112 her keto-1,2,4-oxadiazole inhibitor for GVIA iPLA2, which will serve as lead compounds for future dev

113 inhibitors inhibited either GV sPLA2 or GVIA iPLA2.

114 h higher potency and selectivity toward GVIA iPLA2.

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

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

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

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

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

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

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

122 pathogenesis of Barth syndrome and identify iPLA2-VIA as an important enzyme in cardiolipin deacylat

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

147 A significant increase in iPLA2 activity was observed in WT mice following infecti

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

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

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

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

152 ed by inhibitors of the calcium-independent (iPLA2) form of the enzyme, whereas responses to menthol

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

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

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

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

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

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

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

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

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

162 ages (BMDMs) expressed cPLA2-IVA, cPLA2-IVB, iPLA2-VI, sPLA2-IIE, and sPLA2-XIIA.

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

164 tor abnormalities seen in aged flies lacking iPLA2-VIA gene function, and restore mitochondrial membr

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

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

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

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

169 ia even before apoptotic induction, and most iPLA2-associated mitochondria were intact in apoptotic r

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

208 Whereas the action of iPLA2 is immediate, the action of cPLA2 requires a lag t

209 in Chagas' disease and a known activator of iPLA2, increased AA and PGE2 release, accompanied by pla

210 Expression of iPLA2 in INS-1 cells prevented the loss of mitochondrial

211 eversal of calmodulin-mediated inhibition of iPLA2 beta phospholipase A2 activity.

212 astatic breast cancer cells by inhibition of iPLA2.

213 Furthermore, we demonstrate that loss of iPLA2-VIA function leads to a number of mitochondrial ab

214 Moreover, we show that loss of iPLA2-VIA is strongly associated with increased lipid pe

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

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

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

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

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

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

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

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

223 ate whether group VIA Ca2+-independent PLA2 (iPLA2) plays a role in the protection of mitochondrial f

224 s by inhibition of calcium-independent PLA2 (iPLA2).

225 2g5, 12a, and 12b), cPLA2 isoform (pla2g4a), iPLA2 isoform (pla2g6), and PLA2-receptor (pla2r1) were

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

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

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

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

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

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

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

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

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

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

236 t not iPLA2beta-null VSMC, Ang II stimulates iPLA2 enzymatic activity significantly.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

259 Together, our data indicate that iPLA2 is important for the protection of mitochondrial f

260 These studies indicate that iPLA2-dependent metabolic pathways play an important rol

261 We show that iPLA2-expressing cells were relatively resistant to STS-

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

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

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

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

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

267 The iPLA(2)gamma pathway is cytoprotective.

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

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

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

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

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

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

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

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

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

277 ensively examined through utilization of the iPLA2-selective inhibitor (E)-6-(bromomethylene)-3-(1-na

278 hough in wild-type flies inactivation of the iPLA2-VIA does not affect the molecular composition of c

279 Furthermore we show that the iPLA2-VIA knockout fly model provides a useful platform

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

281 responses to menthol were less sensitive to iPLA2 inhibition.

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

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

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

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

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

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

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

289 IVA cPLA2 and calcium-independent Group VIA iPLA2.

290 PLA2 enzymes: group IVA cPLA2 and group VIA iPLA2.

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

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

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

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

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

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

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

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

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

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

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