Two intracellular signaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth.
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.
Matsumura
T
T
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Sakai
M
M
Kobori
S
S
Biwa
T
T
Takemura
T
T
Matsuda
H
H
Hakamata
H
H
Horiuchi
S
S
Shichiri
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009281:Naphthalenes / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D009281:Naphthalenes; D010566:Virulence Factors, Bordetella; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; C058819:calphostin C; D002118:Calcium