Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes

Biochimica Et Biophysica Acta
Akihiko KuniyasuHitoshi Nakayama

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is secreted from adipose tissue and is considered to be a risk factor for both atherosclerosis and insulin resistance. Here we report for the first time that PAI-1 expression is enhanced by oxidized low-density lipoprotein (OxLDL) and its lipid component lysophosphatidylcholine (LPC) in mouse 3T3-L1 adipocytes. In fully differentiated 3T3-L1 cells, OxLDL treatment increased the mRNA expression and protein secretion of PAI-1 in a dose- and time-dependent manner, whereas native LDL had no effect. The addition of an anti-CD36 antibody suppressed OxLDL-stimulated PAI-1 expression by 50%, suggesting that adipose-derived CD36 contributes to roughly half of the PAI-1 expression stimulated by OxLDL. In addition, pharmacological experiments showed that the OxLDL-stimulated enhancement in PAI-1 expression was mediated through the generation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinase 1/2. Furthermore, LPC, a major lipid component of OxLDL, was responsible for the enhanced expression of PAI-1 as phospholipase A(2)-treated acetyl LDL, which generates LPC, strongly stimulated PAI-1 expression, whereas acetyl LDL itself had no such activity. These dat...Continue Reading

Citations

Oct 1, 2011·Lipids in Health and Disease·Isis T SilvaNágila R T Damasceno
Jul 19, 2012·International Journal of General Medicine·Shosaku NomuraTomoki Ito
Mar 9, 2019·International Journal of Molecular Sciences·Shi-Hui LawLiang-Yin Ke
Nov 13, 2014·Journal of Thrombosis and Thrombolysis·Mohamed Mahmoud El-SeweidyMohamed Ahmed Abdallah
Feb 6, 2020·The Journal of Clinical Endocrinology and Metabolism·Jinnan LiuXilin Yang
Jun 17, 2020·Journal of Cellular and Molecular Medicine·Lumin ChenWei-Chun Chang

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