Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U‐937 macrophage‐like cells

[摘要]

Mitogen activated protein kinase in extracts of U-937 macrophage-like cells was stimulated by LDL and oxLDL. A maximum value (161% of the basal phosphotransferase activity) was obtained after 6 min exposure to oxidized LDL (27 μ/ml) using APRTPGGRR peptide substrate. The activatory effect was more pronounced (LDL 181%, oxLDL 201%) when MAPK of stimulated cells was immunoprecipitated with anti-p42^MAPK antibodies and phosphotransferase activity was assayed in immune complexes. Stimulation produced by oxLDL was inhibited by poly I, fucoidan, dextran sulfate and by the MAPKK inhibitor PD 098059 but not by PMA-mediated depletion of PKC or by pre-treatment with chloroquine or with pertussis toxin. These results suggest a direct mitogenic effect of LDL which, in the case of oxLDL, is dependent on scavenger receptor ligation but not on G-protein mediated or PKC-dependent signal transduction.

[学科分类] 生物化学/生物物理

[关键词] Mitogen activated protein kinase;Lipoprotein;Oxidized LDL;U937 cells;BSA;bovine serum albumin;LysoPAF;1-O-hexadecyl-sn-glycero-3-phosphocholine;MAP-kinase (MAPK);mitogen activated protein kinase;ERK;extracellular signal-regulated kinases;MAPKK;MAPK/ERK kinase;MEK;MAPK-activating enzyme;acLDL;acetylated low density lipoprotein;oxLDL;oxidized LDL;MBP;myelin basic protein;malBSA;maleylated bovine serum albumin;PAF;platelet activating factor;1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine;poly I;polyinosinic acid;PLA2;phospholipase A2;PKC;protein kinase C;PMA;phorbol-12-myristate-13-acetate;SR;scavenger receptor