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Use of protein kinase A inhibitor in preparation of medicament for treating diseases related to increase of number of platelets

A technology of thrombocytosis and protein kinase, which is applied in the field of platelet-related drugs to achieve the effect of reducing the number and reducing the number of

Inactive Publication Date: 2018-07-31
SUZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, whether PKA has a greater effect on platelet apoptosis induced by storage or pathological stimuli remains unknown.

Method used

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  • Use of protein kinase A inhibitor in preparation of medicament for treating diseases related to increase of number of platelets
  • Use of protein kinase A inhibitor in preparation of medicament for treating diseases related to increase of number of platelets
  • Use of protein kinase A inhibitor in preparation of medicament for treating diseases related to increase of number of platelets

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Embodiment Construction

[0031] 1. Reagents and materials:

[0032]Anti-GpIIb / IIIa monoclonal antibody SZ21 was provided by Professor Ruan Changgeng, Director of Jiangsu Institute of Hematology, dimethyl sulfoxide (DMSO) and anti-Actin primary antibody were purchased from Sigma, USA, and EDTA-K2 anticoagulant tubes were purchased from BD, USA Company, fluorescein isothiocyanate (Fluorescein Isothiocyanate, FITC)-Annexin V was purchased from Beijing Jiamei Biotechnology Co., Ltd., FITC-goat anti-mouse antibody was purchased from American Bioworld Technology Company, (Horse Radish Peroxidase, HRP)-goat anti-mouse , HRP-goat anti-rabbit, rabbit and mouse IgG, anti-BAX, anti-BAK, anti-Bcl-xL, anti-Bcl-2, anti-Caspase-3, anti-BAD155 phosphorylated antibodies were purchased from Santa Cruz Biotechnology Company, USA, anti-PKA Cα Antibodies were purchased from CST, USA; N-[2-((p-Bromocinnamyl) amino)ethyl]-5-isoquinolinesulfonamide (H89), Forsklin, anti-GAPDH, anti-P53 antibodies, JC-1, ECL, and PMSF were pu...

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Abstract

The present invention discloses use of a protein kinase A inhibitor in preparation of a medicament for treating diseases related to increase of number of platelets. The method, for the first time, explores the role of protein kinase A in regulation of platelet apoptosis process. Studies show that by inhibition of the activity of the protein kinase A, endogenous platelet apoptosis can be caused. The studies suggest that the PKA inhibitor has the effect of promoting the platelet apoptosis, and the protein kinase A regulates the platelet apoptosis by regulating phosphorylation of serine at 155-site of BAD. The protein kinase A inhibitor can cause the platelet apoptosis in in-vitro experiments, and also can cause reduction of the number of the platelets in experimental animals. The number of circulating platelets in the body of a protein kinase A gene-knockout mouse is reduced, so that the protein kinase A inhibitor has a potential for development of new drugs for treatment of thrombocytosis diseases, and is of great scientific research and economic value.

Description

technical field [0001] The invention belongs to the field of platelet-related drugs, and in particular relates to the use of protein kinase A inhibitors in the preparation of drugs for treating diseases related to increased platelet count. Background technique [0002] Platelets are the key factors regulating thrombus formation and pathological hemorrhage in the circulatory system, and also play an important role in the body's immune response, infection, atherosclerosis formation, and tumor metastasis and other pathophysiological processes. The fine regulation of the life cycle of platelets is the key to maintaining the number of platelets in a normal human body. Increased platelets are seen in many diseases, such as essential thrombocythemia and polycythemia vera. In some pathological processes, the number of peripheral blood platelets increases. Increased risk of bleeding or thrombosis, such as chronic myelogenous leukemia, post-hemorrhage and chronic inflammation, tumor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/551A61K31/7076A61P35/02A61P35/00A61P31/00A61P37/02A61P19/08A61P7/04A61P7/02
CPCA61K31/551A61K31/7076A61K45/00
Inventor 戴克胜
Owner SUZHOU UNIV
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