摘要
OBJECTIVE:To explore the functional role of the drugdependent mesenchymal-epithelial transition(Met)-axiation"π"structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia.METHODS:We used a Glutathione S-transferase(GST)-pull down assay,isothermal titration calorimetry assay,and other related methods to identify the relationships among Met,inositol polyphosphate phosphatase like 1(Inppl1),and death associated protein kinase 3(Dapk3)in this allosteric module.The biological effects of the modules of neurons generation composed of Met,Inppl1,and Dapk3 were measured through Western blot,apoptosis analysis,and double immunofluorescence labeling.RESULTS:The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex;Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region.Thus,we obtained a“π”structuring module considered a neural regeneration module.The biological effects of angiogenesis and neurogenesis modules composed of Met,Inppl1,and Dapk3 were also verified.CONCLUSION:The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.
基金
National Major Scientific and Technological Special Project for“Significant New Drugs Development”:Clinical Value Prescription Discovery and Evaluation Technology Based on Modular Pharmacology(No.2017ZX09301059)
the Joint Innovation Project of China Academy of Chinese Medical Sciences:Study on the Mechanism of Action of Neuronal Regenerative Function Module Activated by Qingkailing Components(No.ZZ11-026)
the University Collaborative Innovation Project of Anhui:Creation of a Combined Animal Model of Coronary Heart Disease Based on the Theory of Xin'an Medicine(No.GXXT-2020-024)
the University Natural Science Research Project of Anhui Province:Molecular Mechanism of the Anti-hepatic Fibrosis Effect of Wickerwork Amide Based on the Regulation of Intercellular Communication by PTRF(No.2023AH051752)。
