Involvement of Mst1 in tumor necrosis factor-α-induced apoptosis of endothelial cells

Hideki Ohtsubo, Toshihiro Ichiki, Ikuyo Imayama, Hiroki Ono, Kae Fukuyama, Yasuko Hashiguchi, Junichi Sadoshima, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-α-induced apoptosis of ECs. Western blot analysis revealed that TNF-α induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-α-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting of propidium iodide-stained cells showed that TNF-α induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-α-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-α-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-α-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.

Original languageEnglish (US)
Pages (from-to)474-480
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Mar 7 2008

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


  • Apoptosis
  • Caspase 3
  • Mst1
  • Reactive oxygen species
  • TNF-α


Dive into the research topics of 'Involvement of Mst1 in tumor necrosis factor-α-induced apoptosis of endothelial cells'. Together they form a unique fingerprint.

Cite this