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[PMID]: | 28641286 |
[Au] Autor: | Cao H; Bissinger R; Umbach AT; Gawaz M; Lang F |
[Ad] Endereço: | Department of Internal Medicine III, Tuebingen, Germany. |
[Ti] Título: | Effect of Bexarotene on Platelet Activation and Apoptosis. |
[So] Source: | Cell Physiol Biochem;42(2):838-847, 2017. | [Is] ISSN: | 1421-9778 |
[Cp] País de publicação: | Switzerland |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND/AIMS: The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface. Platelet apoptosis is triggered by increase of cytosolic Ca2+-activity ([Ca2+]i), which further leads to degranulation and integrin activation. Platelet activation and apoptosis could be elicited by thrombin or collagen related peptide (CRP). The present study explored whether treatment of platelets with bexarotene modifies platelet activation and apoptosis following exposure to thrombin or CRP. METHODS: Platelets isolated from wild-type mice were exposed for 30 minutes to bexarotene (6 µg/ml) without or with an additional treatment with thrombin (0.01 U/ml) or CRP (2 µg/ml or 5 µg/ml). Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbß3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, and relative platelet volume from forward scatter. RESULTS: In the absence of thrombin or CRP, the administration of bexarotene slightly but significantly increased [Ca2+]i, but did not significantly modify P-selectin abundance, activated αIIbß3 integrin, annexin-V-binding, cell volume, or caspase activity. Exposure of platelets to thrombin or CRP was followed by significant increase of [Ca2+]i, P-selectin abundance, active αIIbß3 integrin, annexin-V-binding, and caspase activity. The effects of thrombin on [Ca2+]i, annexin-V-binding, cell volume, and caspase activity as well as the effects of CRP on [Ca2+]i, P-selectin abundance, activated αIIbß3 integrin, annexin-V-binding, cell volume, and caspase activity were significantly augmented in the presence of bexarotene. CONCLUSIONS: Bexarotene sensitizes blood platelets for thrombin and/or CRP induced activation and apoptosis. |
[Mh] Termos MeSH primário: |
Apoptose/efeitos dos fármacos Ativação Plaquetária/efeitos dos fármacos Tetra-Hidronaftalenos/administração & dosagem Trombina/metabolismo
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[Mh] Termos MeSH secundário: |
Animais Plaquetas/efeitos dos fármacos Plaquetas/metabolismo Cálcio/metabolismo Colágeno/metabolismo Eritrócitos/metabolismo Citometria de Fluxo Hemólise/efeitos dos fármacos Seres Humanos Camundongos Ativação Plaquetária/genética Complexo Glicoproteico GPIIb-IIIa de Plaquetas Espécies Reativas de Oxigênio/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Platelet Glycoprotein GPIIb-IIIa Complex); 0 (Reactive Oxygen Species); 0 (Tetrahydronaphthalenes); 9007-34-5 (Collagen); A61RXM4375 (bexarotene); EC 3.4.21.5 (Thrombin); SY7Q814VUP (Calcium) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 170804 |
[Lr] Data última revisão:
| 170804 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170623 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1159/000478627 |
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