Inhibition of the release of arachidonic acid prevents the development of sarcolemmal membrane defects in cultured rat myocardial cells during adenosine triphosphate depletion.

Abstract

Previous studies have suggested that phospholipid degradation is closely associated with the development of sarcolemmal membrane injury. This study was initiated to characterize the effects of synthetic inhibitors of phospholipase activities using a cultured myocardial cell model in which arachidonic acid is liberated after treatment with the metabolic inhibitor, iodoacetate. Pretreatment with a steroidal diamine (U26,384) blocked the degradation of labeled phosphatidylcholine and the release of arachidonic acid in cultured myocardial cells during ATP depletion. Inhibition of phospholipid degradation by U26,384 prevented the development of sarcolemmal membrane defects and the release of creatine kinase from the cultured myocardial cells during ATP depletion. Pretreatment with U26,384 had no significant effect on the extent of ATP depletion after iodoacetate treatment, which indicates that the activity of this compound could not be simply ascribed to a sparing effect on ATP concentration. These results support the hypothesis that the development of sarcolemmal membrane injury and the associated loss of cell viability are causally related to progressive phospholipid degradation. In addition, these studies indicate that the release of arachidonic acid during ATP depletion is associated with the net loss of the phosphatidylcholine molecule.

Angiotensin II AT1-receptor induces biglycan in neonatal cardiac fibroblasts via autocrine release of TGFβ in vitro

“…Cardiac fibroblasts were isolated from neonatal (2 -3 days old) Wistar Kyoto rats as described previously [14]. The fibroblasts were cultured in DMEM plus 20% fetal calf serum, passaged by use of trypsin, and used for experiments after the first passage.…”

Regulation of K+ channels in cardiac myocytes by free fatty acids.

“…At 50 gM, lysophosphatidylcholine reduced the K' channel activity to below 5% of initial activity in 42±35 seconds (mean+SD, n=4). At 10 ,uM, it took 122±56 seconds (n=3). At Figure 4D.…”

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

“…Phospholipase A 2 (PLA 2 ) catalyzes the hydrolysis of fatty acids at the sn-2 position of membrane phospholipid, yielding free fatty acids (FFAs) and a lysophospholipid as products, and has been proposed to play an important role in cell injury associated with I/R. The PLA 2 -induced changes in phospholipid integrity and the toxic actions of FFAs and lysophospholipids are believed to contribute to tissue injury in the kidney [6], brain [7], heart [8] and intestine [9] ischemia. Besides, reactive oxygen species (ROS) which cause damage to lipid, DNA and protein also contribute to renal I/R injury [10].…”