Lysophosphatidylcholine Stimulates Activator Protein 1 and the c-Jun N-terminal Kinase Activity

Abstract

Lysophosphatidylcholine (lyso-PC), a natural lipid generated through the action of phospholipase A 2 on membrane phosphatidylcholine, has been implicated in atherogenesis and the inflammatory process. In vitro studies have established a role for lyso-PC in modulation of gene expression and other cellular responses including differentiation and proliferation. There is also evidence that lyso-PC may act as an intracellular second messenger transducing signals elicited from membraneassociated receptors. The mechanisms behind the diverse activities of lyso-PC are poorly understood. We report, in this study, that treatment of cultured cells with exogenous lyso-PC, at nontoxic concentrations, potently induced activator protein-1 (AP-1) DNA binding and transcriptional activity independent of well known AP-1 activators, protein kinase C or mitogen-activated protein kinases ERK1 and ERK2. Lyso-PC also activated the c-Jun N-terminal kinase (JNK/SAPK), a recently characterized member of the mitogen-activated protein kinase family, known to activate AP-1. The stimulated JNK and AP-1 activities probably mediate or contribute to some bioactive effects of lyso-PC.

The impact of fat distribution on the severity of nonalcoholic fatty liver disease and metabolic syndrome

“…Several lipid classes are known to promote inflammation. 46,47 It is likely that lipidomic approaches will show if the severity of steatosis is associated with proinflammatory lipids and/or activation of inflammatory signaling. On the other hand, none of the fat distribution patterns correlated with the severity of steatosis.…”

Lysophosphatidylcholine Potentiates the Mitogenic Effect of Various Vasoactive Compounds on Rabbit Aortic Smooth Muscle Cells.

“…33) Our previous study has shown that the mitogenic effect of lyso-PC on rabbit VSMCs is mediated via the redox-sensitive (JNK) pathway rather than via the ERK pathway. 34) TX-A 2 , 5-HT, Ang-II, ET-1, and U-II activate Gq protein-coupled receptors (TP, 5-HT 2A , AT 1 , ET A , or GPR14, respectively)-Src family tyrosine kinase-protein kinase C. [12][13][14]35,36) H 2 O 2 , TX-A 2 , 5-HT, Ang-II, ET-1, and U-II all activate the ERK pathway.…”

Mitogenic Effect of Lipoproteins on Human Vascular Smooth Muscle Cells: The Impact of Hydrolysis by gr II A Phospholipase A2

“…Whereas only a minimal effect was reported (Libby et al 1985), others found that LDL has a definite mitogenic effect (Fang et al, 1997;Locher et al, 1992). The effect was more pronounced when VSMC were cultured in low-serum medium (Chen et al, 1986) or when LDL was oxidized (Heery et al, 1995).…”

“…The impact of LDL on mitogenic activity of VSMC was found to vary, depending on experimental conditions (Chen et al, 1986;Fang et al, 1997;Heery et al, 1995;Leitinger et al, 1999;Libby et al, 1985;Locher et al, 1992;Scott-Burden et al, 1989). Whereas only a minimal effect was reported (Libby et al 1985), others found that LDL has a definite mitogenic effect (Fang et al, 1997;Locher et al, 1992).…”

“…SAA was found to be a cofactor of sPLA 2 , markedly enhancing its hydrolytic activity (Pruzanski et al, 1995). In turn, sPLA 2 hydrolyzes HDL, APHDL, and LDL, releasing lyso-compounds and free fatty acids (Pruzanski et al, 1998), which per se can modify the activity of and may be toxic to a variety of cells (Fang et al, 1997;Kume et al, 1992;Locher et al, 1992;Kaneko et al, 1996;Quinn et al, 1988;Yagi et al, 1996;Yamakawa et al, 1998). APHDL is hydrolyzed by sPLA 2 faster than normal (N)HDL (Pruzanski et al, 1998).…”