[Inhibitory effects of protein kinase C inhibitors on tumor necrosis factor induced bovine pulmonary artery endothelial cell injuries]

Yao Xue Xue Bao. 1996;31(3):176-81.
[Article in Chinese]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology*
  • Animals
  • Cattle
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Female
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Kinase C / antagonists & inhibitors*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / drug effects
  • Quercetin / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Tumor Necrosis Factor-alpha
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • DNA
  • Quercetin
  • L-Lactate Dehydrogenase
  • Protein Kinase C