Natriuretic peptide drugs have become a hot spot for the development of therapeutic drugs in the stage of acute decompensated heart failure. Therefore, the structure, activity, signaling pathways and regulation of natriuretic peptide receptors are studied to explore the efficacy of natriuretic peptide receptors and natriuretic peptides. The connection between them has important theoretical significance and application value. Researchers from the School of Medicine of Jiangnan University recently published a review article that introduced the type, structure, activity regulation, and signaling pathways of natriuretic peptide receptors.
Natriuretic peptides are a group of hormones secreted by cardiomyocytes, mainly including ANP, BNP and CNP. They can act on neighboring cardiomyocytes, vascular smooth muscle cells, etc. through autocrine or paracrine, specific sodium on the target cell membrane. Urinary peptide receptors NPR-A, NPR-B and NPR-C combine to initiate a series of intracellular signal transduction to exert their diuretic, natriuretic, vasodilator, lower blood pressure and regulate electrolyte balance and other physiological functions.
The physiological functions of natriuretic peptides are achieved through the combination with their specific natriuretic peptide receptors (NPRs). Therefore, in-depth research on NPRs will promote the application and new types of NPs drugs in medical research and clinical treatment. NPs have important value in drug development.
The article introduces the types, structure, activity regulation and signaling pathways of NPRs from various aspects. Among them, the researchers pointed out that the expression and biological activity of NPRs are regulated by various factors, such as growth factors and angiotensin â…¡ (Angâ…¡), endothelin, glucocorticoid and NPs etc. Among the three types of NPRs, the most research on the regulation of NPR-A gene transcription level. Kumar et al. Studied the promoters of human and murine NPR-A genes and found that:
(i) A reverse CCAAT box replaces the traditional TATA box; BioCom
(ii) The transcription start site of the human NPR-A gene is located 88 bp upstream of the start codon, while the mouse is located at 362-370 bp at the 5 â€² untranslated region;
(iii) There are multiple elements that can up-regulate or down-regulate its mRNA expression. Three Sp1 binding sites drive transcriptional activity. Mutation at any one site will reduce the promoter activity by 50%. If all three sites are deleted, it will result in Promoter activity decreased by 90%;
(iV) There is a cGMP response element (cGMP-RE) in the promoter, which can down-regulate the expression of NPR-A gene through the combination with cGMP to achieve the negative feedback regulation of cGMP ;
(V) The promoter of the mouse NPR-A gene includes a TA repeat, and the number of TAs is inversely proportional to the expression level of NPR-A. Biocom
With the deepening of research on the structure, function and activity regulation of NPRs, some researchers have tried to use computational biology technology to design and screen new, efficient, safe and stable new NPs drugs by transforming natural NPs molecules. The study of the crystal structure of the membrane region and the intracellular region is not thorough enough. The mechanism of the interaction between NPRs and NPs is still controversial. There are also unknown regulatory factors in the NPs-NPRs signaling pathway, which are all ideal drugs for NPs. Design and development pose obstacles.
The article finally pointed out that with the in-depth study of NPRs, especially from the perspective of the relationship between the structure and function of NPRs complexes, and the regulation of signal expression, understanding the role of NPs in vivo will help to explore cardiovascular diseases, especially hypertension The pathophysiological mechanism of heart failure has opened up new ideas for clinical diagnosis and treatment and the development of new NP drug molecules.
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