Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3013-3020
© 1997 American Heart Association, Inc.
Articles |
Two Intracellular Signaling Pathways for Activation of Protein Kinase C Are Involved in Oxidized Low-Density Lipoprotein–Induced Macrophage Growth
From the Departments of Metabolic Medicine (T.M., M.S., S.K., T.B., T.T., H.M., M.S.) and Biochemistry (H.H., S.H.), Kumamoto University School of Medicine, Kumamota, Japan.
Correspondence to Takeshi Matsumura, MD, Department of Metabolic Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860, Japan.
Abstract Recent studies demonstrated that oxidized LDL (Ox-LDL) induces macrophage growth in vitro. The present study was undertaken to elucidate the intracellular signaling pathways for macrophage growth. Ox-LDL initiated a rapid and transient rise in intracellular free calcium ion and induced activation of membrane protein kinase C (PKC). Pertussis toxin completely inhibited the Ox-LDL–induced rise in free calcium ion and significantly inhibited macrophage growth by 50%. Moreover, PKC inhibitors calphostin C and H-7 significantly inhibited Ox-LDL–induced macrophage growth by 80%. On the other hand, phospholipase A2–treated acetylated LDL did not induce a rise in calcium but significantly activated PKC and led to significant macrophage growth that was significantly inhibited by calphostin C by 90%. These results suggest the presence of two intracellular signaling pathways for activation of PKC, a rise in calcium that was mediated by pertussis toxin–sensitive G protein and the internalization of lysophosphatidylcholine through the scavenger receptors. These two pathways may play an important role in Ox-LDL–induced macrophage growth.
Key Words: protein kinase C • G proteins • oxidized LDL • macrophage growth • atherosclerosis
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