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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Article
Author(s)
Yuan-Han Yang, Hsueh-Wei Chang, Wei-Chiao Chang, Yu-Cheng Shih, Ke-Li Tsai, I Chien and Shyh-Jong Wu
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DOI:10.17265/2328-2150/2016.08.010
Affiliation(s)
ABSTRACT
The ACE (angiotensin converting enzyme) inhibitors are
not only drugs widely prescribed drugs in cardiovascular diseases, but also
potentially therapeutic agents in dementia. Based on the findings that the ACE
inhibitors could activate the c-Jun N-terminal kinase signal to increase the
ACE gene expression and that the Alu element of
the human ACE gene involved in regulating ACE promoter activity, we aimed to
investigate whether there are different pharmacogenetic responses of ACE I/D
polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro(f)-SEAP,
p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the
lisinopril treatment using a transient-transfection method in SH-SY5Y cells.
Our results showed that lisinopril increased the promoter activity of an ACE
gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%,
but adversely reduced that of the D-form vector by 16.8%, as compared with the
respective control without the lisinopril treatment. Firstly, our findings had proved that the I/D polymorphism of ACE gene
contrarily responds to the ACE inhibitors in regulating the ACE expression in
neurons, which provide a novel insight suggesting genetic
testing to tailor the treatment regimens in AD (Alzheimer’s disease) patients.
KEYWORDS
ACE inhibitors, ACE I/D polymorphism, Alzheimer’s disease, pharmacogenetics, promoter activity.
Cite this paper
Yang, Y-H., et al. 2016. “Pharmarcogenetic Mechanism of ACE I/D Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons.” Journal of Pharmacy and Pharmacology 4 (8): 419-431.
References