Examining the Interactome of Huperzine A by Magnetic Biopanning

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 May 23

PMID 22615909

Citations 2

Authors

Wei Guo

Shupeng Liu

Jinliang Peng

Xiaohui Wei

Ye Sun

Yangsheng Qiu

Guangwei Gao

Peng Wang

Yuhong Xu

Affiliations

Soon will be listed here.

Abstract

Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules.

Citing Articles

Interaction analysis through proteomic phage display.

Sundell G, Ivarsson Y Biomed Res Int. 2014; 2014:176172.

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Kushwaha R, Payne C, Downie A Comput Math Methods Med. 2013; 2013:653759.

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