endothelin-1;
protein carbonylation;
oxidant signaling;
pulmonary hypertension;
smooth muscle;
D O I:
10.1161/CIRCRESAHA.107.159814
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Reactive oxygen species serve as second messengers for signal transduction; however, molecular targets of oxidant signaling have not been defined. Here, we show that ligand-receptor-mediated signaling promotes reactive oxygen species-dependent protein carbonylation. Treatment of pulmonary artery smooth muscle cells with endothelin-1 increased protein carbonyls. Carbonylation of the majority of proteins occurred transiently, suggesting that there is also a mechanism for decarbonylation induced by endothelin-1. Decarbonylation was suppressed by inhibition of thioredoxin reductase, and cellular thioredoxin was upregulated during the decarbonylation phase. These results indicate that endothelin-1 promotes oxidant signaling as well as thioredoxin-mediated reductive signaling to regulate carbonylation and decarbonylation mechanisms. In cells treated with endothelin receptor antagonists, hydrogen peroxide scavengers, or an iron chelator, we identified, via mass spectrometry, proteins that are carbonylated in a receptor- and Fenton reaction-dependent manner, including annexin A1, which promotes apoptosis and suppresses cell growth. Carbonylation of annexin A1 by endothelin-1 was followed by proteasome-dependent degradation of this protein. We propose that carbonylation and subsequent degradation of annexin A1 may play a role in endothelin-mediated cell growth and survival, important events in pulmonary vascular remodeling. Protein carbonylation in response to ligand-receptor interactions represents a novel mechanism in redox signaling.
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Lee, SL
;
Simon, AR
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Simon, AR
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Wang, WW
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Lee, SL
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Wang, WW
;
Finlay, GA
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Finlay, GA
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
Lee, SL
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
Wang, WW
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England
Moran, LK
;
Gutteridge, JMC
论文数: 0引用数: 0
h-index: 0
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England
Gutteridge, JMC
;
Quinlan, GJ
论文数: 0引用数: 0
h-index: 0
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Lee, SL
;
Simon, AR
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Simon, AR
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
Wang, WW
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Tupper Res Inst,Pulm & Crit Care Div, Boston, MA 02111 USA
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Lee, SL
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Wang, WW
;
Finlay, GA
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
Finlay, GA
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USATufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
Lee, SL
;
Wang, WW
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
Wang, WW
;
Fanburg, BL
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USATufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div,Tupper Res Inst, Boston, MA 02111 USA
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England
Moran, LK
;
Gutteridge, JMC
论文数: 0引用数: 0
h-index: 0
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England
Gutteridge, JMC
;
Quinlan, GJ
论文数: 0引用数: 0
h-index: 0
机构:
Royal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, EnglandRoyal Brompton Hosp, Imperial Coll, Sch Med, Crit Care Unit, London SW3 6NP, England