• Inicio
  • Resultados de la búsqueda
  • Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.

Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.

Free radical biology & medicine (2015-02-04)
Su Bin Wang, Ji Yong Jang, Yun Hee Chae, Ji Hyun Min, Jin Young Baek, Myunghee Kim, Yunjeong Park, Gwi Seo Hwang, Jae-Sang Ryu, Tong-Shin Chang
RESUMEN

Reactive oxygen species (ROS) generated upon collagen stimulation act as second messengers to propagate various platelet-activating events. Among the ROS-generating enzymes, NADPH oxidase (NOX) plays a prominent role in platelet activation. Thus, NOX has been suggested as a novel target for anti-platelet drug development. Although kaempferol has been identified as a NOX inhibitor, the influence of kaempferol on the activation of platelets and the underlying mechanism have never been investigated. Here, we studied the effects of kaempferol on NOX activation, ROS-dependent signaling pathways, and functional responses in collagen-stimulated platelets. Superoxide anion generation stimulated by collagen was significantly inhibited by kaempferol in a concentration-dependent manner. More importantly, kaempferol directly bound p47(phox), a major regulatory subunit of NOX, and significantly inhibited collagen-induced phosphorylation of p47(phox) and NOX activation. In accordance with the inhibition of NOX, ROS-dependent inactivation of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) was potently protected by kaempferol. Subsequently, the specific tyrosine phosphorylation of key components (Syk, Vav1, Btk, and PLCγ2) of collagen receptor signaling pathways was suppressed by kaempferol. Kaempferol also attenuated downstream responses, including cytosolic calcium elevation, P-selectin surface exposure, and integrin-αIIbβ3 activation. Ultimately, kaempferol inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. This study shows that kaempferol impairs collagen-induced platelet activation through inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2. This effect suggests that kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Glycerol, for molecular biology, ≥99.0%
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)
Sigma-Aldrich
Citric acid, ACS reagent, ≥99.5%
Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Glycerol, ≥99.5%
Sigma-Aldrich
D-(+)-Glucose, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Potassium phosphate monobasic, powder, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Iodoacetamide, BioUltra
Sigma-Aldrich
Citric acid, 99%
Sigma-Aldrich
Dextrose, meets EP, BP, JP, USP testing specifications, anhydrous
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
D-(+)-Glucose, ACS reagent
Sigma-Aldrich
Potassium phosphate monobasic, ReagentPlus®
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
N-Ethylmaleimide, crystalline, ≥98% (HPLC)
Sigma-Aldrich
Iodoacetamide, Single use vial of 56 mg
Sigma-Aldrich
Iodoacetamide, ≥99% (NMR), crystalline
Sigma-Aldrich
D-(+)-Glucose, BioXtra, ≥99.5% (GC)
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Potassium phosphate monobasic, for molecular biology, ≥98.0%
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Sigma-Aldrich
Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
Glycerin, meets USP testing specifications
Sigma-Aldrich
Kaempferol, ≥97.0% (HPLC)
Sigma-Aldrich
4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride, ≥97.0% (HPLC)
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)