| First Author | Bao S | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 37 | Pages | 27100-14 |
| PubMed ID | 17627946 | Mgi Jnum | J:172112 |
| Mgi Id | MGI:5003433 | Doi | 10.1074/jbc.M701316200 |
| Citation | Bao S, et al. (2007) Attenuated free cholesterol loading-induced apoptosis but preserved phospholipid composition of peritoneal macrophages from mice that do not express group VIA phospholipase A2. J Biol Chem 282(37):27100-14 |
| abstractText | Mouse macrophages undergo ER stress and apoptosis upon free cholesterol loading (FCL). We recently generated iPLA(2)beta-null mice, and here we demonstrate that iPLA(2)beta-null macrophages have reduced sensitivity to FCL-induced apoptosis, although they and wild-type (WT) cells exhibit similar increases in the transcriptional regulator CHOP. iPLA(2)beta-null macrophages are also less sensitive to apoptosis induced by the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin and the scavenger receptor A ligand fucoidan, and restoring iPLA(2)betaexpression with recombinant adenovirus increases apoptosis toward WT levels. WT and iPLA(2)beta-null macrophages incorporate [(3)H]arachidonic acid ([(3)H]AA]) into glycerophosphocholine lipids equally rapidly and exhibit identical zymosan-induced, cPLA(2)alpha-catalyzed [(3)H]AA release. In contrast, although WT macrophages exhibit robust [(3)H]AA release upon FCL, this is attenuated in iPLA(2)beta-null macrophages and increases toward WT levels upon restoring iPLA(2)beta expression. Recent reports indicate that iPLA(2)beta modulates mitochondrial cytochrome c release, and we find that thapsigargin and fucoidan induce mitochondrial phospholipid loss and cytochrome c release into WT macrophage cytosol and that these events are blunted in iPLA(2)beta-null cells. Immunoblotting studies indicate that iPLA(2)beta associates with mitochondria in macrophages subjected to ER stress. AA incorporation into glycerophosphocholine lipids is unimpaired in iPLA(2)beta-null macrophages upon electrospray ionization-tandem mass spectrometry analyses, and their complex lipid composition is similar to WT cells. These findings suggest that iPLA(2)beta participates in ER stress-induced macrophage apoptosis caused by FCL or thapsigargin but that deletion of iPLA(2)beta does not impair macrophage arachidonate incorporation or phospholipid composition. |
