[Inhibitory effects of protein kinase C inhibitors on tumor necrosis factor induced bovine pulmonary artery endothelial cell injuries].
The effects of protein kinase C(PKC) inhibitors 1-(5-isoquino-linylsulfonyl)-2-methylpeperazine (H-7) and quercetin on tumor necrosis factor (TNF) were studied in cultured bovine pulmonary artery endothelial cells (BPAEC) in vitro. Incubation of BPAEC with TNF caused a significant increase in percent lactate dehydrogenase (LDH) release, stimulation of EC-dependent neutrophils (PMN) adhesion to BPAEC and inhibition of BPAEC DNA synthesis and proliferation. All these were restored by both H-7 and quercetin. The IC50 of H-7 and quercetin was 9.7 and 10.8 mumol.L-1 for the inhibition of LDH% release; 19.5 and 16.7 mumol.L-1 for the inhibition of TNF-induced PMN-EC adhesion; 7.0 and 6.1 mumol.L-1 for TNF-induced inhibition of DNA synthesis and 8.7 and 11.36 mumol.L-1 for proliferation. These results suggest that PKC inhibitors H-7 and quercetin protect BPAEC from TNF induced injuries and PKC play an important role in EC activation by TNF.
Yu
X B
XB
Department of Pharmacology, Fuzkou General Hospital.
Liu
X J
XJ
Qian
D H
DH
Zhang
J P
JP
Hu
Z L
ZL
Wu
T M
TM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D014409:Tumor Necrosis Factor-alpha; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C