title: Evidence that lipoproteins are carriers of bioactive factors.
abstract: We recently demonstrated that the mitogenic effect of LDL (100 microg/mL) as well as its early intracellular signaling pathway are mediated by a pertussis-toxin (PTX)-sensitive G(i) protein-coupled receptor that is independent from its classical receptor and involves activation of extracellular response kinases (ERK1/2) (also known as p44(mapk)/p42(mapk)). In the present study we examined whether LDL-adherent factors may be responsible for some of the effects of LDL. The term "signaling activity" is used to characterize fractions that cause an increase in intracellular free Ca(2+) concentration or stimulate ERK1/2 and c-fos mRNA expression. LDL, HDL, and VLDL stimulate ERK1/2 with the following order of potency: LDL>HDL>VLDL. After delipidation of LDL with chloroform/methanol/water mixtures a PTX-sensitive signaling activity was found in one fraction arbitrarily called LDL-F. After further analysis of LDL-F compounds by high pressure liquid chromatography, a PTX-sensitive signaling activity was detected only in the fraction with a retention time of 33 minutes (arbitrarily called LDL-F33). Similarly, after separation of sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPC) by high pressure liquid chromatography, a PTX-sensitive signaling activity was found in the fractions 33 and 33 to 35, respectively. These findings demonstrate that the effects of LDL-F33 are mimicked by similar fractions collected from SPP/SPC, hence suggesting that these LDL-adherent molecules are possibly closely related to SPP/SPC. A PTX-sensitive signaling activity was also detected in HDL and HDL-F33. Therefore, LDL and other lipoproteins may function as carriers for bioactive phospholipids thereby contributing to the development of coronary artery disease. Our findings support a new research concept that may contribute in elucidating cellular mechanisms promoting coronary artery disease.
authors.affiliation: Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, Bonn, Germany. sachinidis@uni-bonn.de
authors.forename: A
authors.initials: A
authors.lastname: Sachinidis
authors.forename: R
authors.initials: R
authors.lastname: Kettenhofen
authors.forename: S
authors.initials: S
authors.lastname: Seewald
authors.forename: I
authors.initials: I
authors.lastname: Gouni-Berthold
authors.forename: U
authors.initials: U
authors.lastname: Schmitz
authors.forename: C
authors.initials: C
authors.lastname: Seul
authors.forename: Y
authors.initials: Y
authors.lastname: Ko
authors.forename: H
authors.initials: H
authors.lastname: Vetter
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002458:Cell Fractionation; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000032:analysis / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000032:analysis / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D037342:Pertussis Toxin; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D004247:DNA; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium