Activation of a novel form of phospholipase A₂ during liver regeneration

Abstract

Activation of phospholipase A2 (PLA2) occurs following mitogenic stimulation of cells. This study examined PLA2 activation during liver regeneration. Increased activity was detected within 1 h after partial hepatectomy, was maximal by 6 h, and returned to control levels by 24 h. Fractionation of cell-free extracts revealed multiple peaks of PLA a activity. One peak appeared identical to the previously described cPLA2, and was modestly stimulated during regeneration. A higher molecular weight form (hPLA2) was stimulated ~5-fold during regeneration. This enzyme was Ca2+-dependent and selective for arachidonoylphosphatidylethanolamine. The activation of this novel form of PLA2 represents an early event in liver regeneration, and is likely to contribute to the proliferative response.

Cytosolic 85-kDa Phospholipase A2-mediated Release of Arachidonic Acid Is Critical for Proliferation of Vascular Smooth Muscle Cells

“…The VSMC hyperplasia evident in atherosclerotic and restenotic vessels is believed to be part of a sequelae of responses to vascular injury by numerous agents including viruses, caustic by-products of cigarettes, hypercholesterolemia, and physical injury. PLA 2 activation has been associated with cellular injury in kidney, heart and liver (71). It remains to be determined if cellular injury specifically alters 85-kDa PLA 2 expression and activity and if the 85-kDa PLA 2 is up-regulated in atherosclerotic or restenotic vessels.…”

“…Alternatively, or additionally, recent reports indicate that the release of AA by PLA 2 is accompanied by the formation of biologically active lysolipids, and that lysophosphatidic acid, lysophosphatidylinositol, and lysophosphatidylcholine stimulate mitogen-activated protein kinase activity and proliferation in a variety of cell types (67)(68)(69)(70)(71). Furthermore, these lysolipids serve as precursors to a new class of biologically active lipid derivatives, the glycerophosphoinositides, which show evidence of being accumulated specifically in ras-transformed cells.…”

85-kDa cPLA2plays a critical role in PPAR-mediated gene transcription in human hepatoma cells

“…In addition to cPLA 2 , accumulating evidence also shows that other forms of PLA 2 s, including type II secretory PLA 2 (sPLA 2 ), may also participate in the release of AA release in various types of cells. Numerous studies have documented the involvement of AA metabolites, PGs, and leukotrienes in various liver physiological and pathophysiological processes including liver regeneration, growth regulation of hepatocytes, inflammation, cirrhosis, and hepatocytic ischemic/hypoxic injuries (31,36,37,49,51,53,59). However, the detailed mechanisms for their actions and the regulation of the key eicosanoid-forming enzymes in liver tissue or liver cells are not well understood.…”

Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice

“…A subclass of down-regulated genes, connected with cholesterol metabolism and isoprenoid synthesis, such as farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS) and Cyp7 were also observed. In the group of genes that was found to be down-regulated in the liver of HBxtransgenic mice, we observed several genes like SAA3, aldolase A, creatine kinase, phospholipase A2 that have been reported elsewhere as up-regulated during the course of liver regeneration [22][23][24] . Interestingly, down-regulation of histone deacetylase and up-regulation of DNA repair genes (Rad52 and MSH6) observed in our study in HBx-transgenic mice after PH have, in agreement with other reports, similar effect on the cell cycle by inducing cell cycle arrest [25][26][27][28] .…”