Activation of PLA₂ isoforms by cell swelling and ischaemia/hypoxia

Abstract

Phospholipase A2 (PLA2) activity is increased in mammalian cells in response to numerous stimuli such as osmotic challenge, oxidative stress and exposure to allergens. The increased PLA2 activity is seen as an increased release of free, polyunsaturated fatty acids, e.g. arachidonic acid and membrane-bound lysophospholipids. Even though arachidonic acid acts as a second messenger in its own most mammalian cells seem to rely on oxidation of the fatty acid into highly potent second messengers via, e.g. cytochrome P450, the cyclo-oxygenase, or the lipoxygenase systems for downstream signalling. Here, we review data that illustrates that stress-induced PLA2 activity involves various PLA2 subtypes and that the PLA2 in question is determined by the cell type and the physiological stress condition.

Physiology of Cell Volume Regulation in Vertebrates

“…800). Similarly, H 2 O 2 potentiates melittin-induced taurine release under isotonic conditions, yet not under hypertonic conditions (503). Thus further stimulation of arachidonic acid release by mellitin and H 2 O 2 requires that a PLA 2 is already active, which is not the case in shrunken cells.…”

“…Pharmacological evidence indicates that the swelling-induced arachidonic acid release and RVD involves cPLA 2 in EAT cells (490,989) and CHP-100 neuroblastoma cells (47), iPLA 2 and sPLA 2 in NIH3T3 cells (492,503,800), and a Ca 2ϩ -dependent PLA 2 activity in rat inner medullar collecting duct cells (996). The mechanism(s) underlying the regulation of PLA 2 activity by osmotic stress remains incompletely elucidated.…”

“…B) PLA 2 IN CELL VOLUME REGULATION. PLA 2 -mediated hydrolysis of phospholipids to free fatty acids and lysophospholipids has been demonstrated to be an essential event in the swelling-induced signaling cascade that leads to osmolyte release in a variety of cell types, including EAT cells (989), human platelets (620), mudpuppy RBCs (566), CHP-100 neuroblastoma cells (47), HeLa cells (504), and NIH3T3 cells (492,503,800). Addition of the bee venom melittin, which increases the substrate availability for the PLA 2 (104), stimulates arachidonic acid mobilization (compare Fig.…”

HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange

“…Ca 2ϩ -independent phospholipase A 2 (iPLA 2 -VI) hydrolyzes the sn-2 esterbond in membrane phospholipids, resulting in release of a free fatty acid and a lysophospholipid such as lysophosphatidylcholine or lysoplasmenylcholine (LPlsCho). We and others have demonstrated that iPLA 2 -VI exerts important effects on the integrity and composition of plasma membrane and organellar membranes, and in cellular signaling processes regulating cell migration, cell volume regulation, inflammation, necrosis, and programmed cell death (PCD) (26,35,42,47,48,53,60). Hypoxia/ischemia and subsequent reperfusion has been found to increase iPLA 2 -VI activity in, e.g., kidney (46), skeletal muscle (47,48), and PC12 cells (53), whereas in the heart, both activation (33,59) and inhibition (57) of iPLA 2 -VI in response to ischemiareperfusion (I/R) have been reported.…”

Arachidonic acid potentiates hypoxia-induced VEGF expression in mouse embryonic stem cells: involvement of Notch, Wnt, and HIF-1α

“…In addition, it is generally assumed that living organisms respond to reduced oxygen concentrations in a cell type-and tissuespecific manner. Hypoxia also increases the release of fatty acids, including arachidonic acid (AA), in a wide variety of cell types (22,28), which participates, either directly or indirectly, in many cellular processes including the regulation of ion channels, cytokine synthesis, cell growth, eicosanoid metabolism, apoptosis, secretion, and regulation of gene expression and is also essential for neonatal growth (7,35). Although the role of signaling molecules in VEGF expression may be cell type and/or stimulus-specific, little or no information exists regarding interactions among the signaling pathways involved in proliferation of mouse embryonic stem (ES) cells under hypoxia.…”