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 language | English |
|---|---|
| Pages (from-to) | 498-501 |
| Number of pages | 4 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 297 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2002 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Inhibition of cGMP-dependent protein kinases potently decreases neutrophil spontaneous apoptosis
AU - Brunetti, Mauro
AU - Mascetra, Nicola
AU - Manarini, Stefano
AU - Martelli, Nicola
AU - Cerletti, Chiara
AU - Musiani, Piero
AU - Aiello, Francesca B.
AU - Evangelista, Virgilio
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Apoptosis
KW - cGMP-dependent protein kinases
KW - Neutrophils
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0036387180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036387180&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(02)02246-5
DO - 10.1016/S0006-291X(02)02246-5
M3 - Article
C2 - 12270121
AN - SCOPUS:0036387180
VL - 297
SP - 498
EP - 501
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -