Regulation of Mitogen-Activated Protein Kinase Cascades by Low Density Lipoprotein and Lysophosphatidic Acid
In: Cellular Physiology and Biochemistry, Jg. 14 (2004), S. 167-176
Online
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Zugriff:
Aim of the present study was to elucidate the regulation of the mitogen activated protein (MAP) kinase cascades as well as the cross-talk between the various MAP kinase isoforms (ERK1/2, SAPK and p38) after stimulation of vascular smooth muscle cells (VSMC) with low density lipoprotein (LDL), 100 microg/ml or lysophosphatidic acid (LPA), 5 microg/ml. Furthermore, the role of the intracellular free Ca(2+) concentration ([Ca(2+)](i)) on the activation of the MAP kinase isoforms as well as on the protein expression of MAP kinase phosphatase (MKP)-1 was investigated. The methods used were Western blot analysis, immunoprecipitation and LDL isolation. Involvement of G(i)-proteins on LDL- and LPA-induced activation of the MAP kinase isoforms was examined by treatment of VSMC with pertussis toxin (PTX),100 ng/ml. LDL as well as LPA induced an activation of SAPK and p38 MAP kinase in a PTX-sensitive manner. The ERK1/2, SAPK and p38 MAP kinase activation was a Ca(2+)-dependent process, most likely regulated through modulation of MKP-1 protein expression. Inhibition of ERK1/2 by PD 98059 completely abolished LDL- and LPA-induced activation of SAPK, whereas the activation of p38 MAP kinase was not affected. We conclude, that [Ca(2+)](i) regulates the PTX-sensitive LDL- and LPA-induced stimulation of the MAP kinase cascades, probably via inhibition of the MKP-1 protein expression.
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Regulation of Mitogen-Activated Protein Kinase Cascades by Low Density Lipoprotein and Lysophosphatidic Acid
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Autor/in / Beteiligte Person: | Sachinidis, Agapios ; Seewald, Stefan ; Hescheler, Jürgen ; Gouni-Berthold, Ioanna |
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Zeitschrift: | Cellular Physiology and Biochemistry, Jg. 14 (2004), S. 167-176 |
Veröffentlichung: | S. Karger AG, 2004 |
Medientyp: | unknown |
ISSN: | 1421-9778 (print) ; 1015-8987 (print) |
DOI: | 10.1159/000078108 |
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