Inhibition of cGMP-dependent protein kinases potently decreases neutrophil spontaneous apoptosis

Mauro Brunetti, Nicola Mascetra, Stefano Manarini, Nicola Martelli, Chiara Cerletti, Piero Musiani, Francesca B. Aiello, Virgilio Evangelista

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The signalling pathways mediating neutrophil spontaneous apoptosis are still largely unknown. We report that the indolocarbazole compound KT5823, a specific inhibitor of cGMP-dependent protein kinases (cGK), dose-dependently inhibited spontaneous apoptosis of neutrophils. At the concentration eliciting the maximum effect (8 μM), it decreased apoptosis from 72.42 ± 12.79% to 45.86 ± 7.22% (p = 0.0002, n = 6). Similarly, the isoquinoline sulfonamide compound H89, another cGK inhibitor, prevented neutrophil apoptosis. At the concentration eliciting the maximum effect (20 μM), it decreased apoptosis from 72.42 ± 12.79% to 31.84 ± 10.70% (p = 0.0004, n = 6). The maximum effect of KT5823 and H89 was comparable to that of GM-CSF and LPS, respectively. Moreover, YC-1, a soluble guanylate cyclase activator, and 4-{[3′,4′,-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline, a specific phosphodiesterase 5 inhibitor, enhanced neutrophil apoptosis, and their effect was antagonised by KT5823. Taken together, these observations highlight a new role of cGK as important mediators of neutrophil spontaneous apoptosis.

Original languageEnglish
Pages (from-to)498-501
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume297
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Neutrophils
Apoptosis
Phosphodiesterase 5 Inhibitors
Guanylate Cyclase
Sulfonamides
Protein Kinase Inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor

Keywords

  • Apoptosis
  • cGMP-dependent protein kinases
  • Neutrophils
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibition of cGMP-dependent protein kinases potently decreases neutrophil spontaneous apoptosis. / Brunetti, Mauro; Mascetra, Nicola; Manarini, Stefano; Martelli, Nicola; Cerletti, Chiara; Musiani, Piero; Aiello, Francesca B.; Evangelista, Virgilio.

In: Biochemical and Biophysical Research Communications, Vol. 297, No. 3, 2002, p. 498-501.

Research output: Contribution to journalArticle

Brunetti, Mauro ; Mascetra, Nicola ; Manarini, Stefano ; Martelli, Nicola ; Cerletti, Chiara ; Musiani, Piero ; Aiello, Francesca B. ; Evangelista, Virgilio. / Inhibition of cGMP-dependent protein kinases potently decreases neutrophil spontaneous apoptosis. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 297, No. 3. pp. 498-501.
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