[Frontiers In Bioscience, Landmark, 22, 1427-1438, March 1, 2017]

TRPM2: a potential drug target to retard oxidative stress

Jun Li1, 4, †, Yunling Gao2, †, Xianying Bao1, 3, Fengna Li1, Wei Yao5, Zemeng Feng1, 6, *, Yulong Yin1

1Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, Hunan 410125, Peoples R China, 2Xiangyang Central Hospital, the Affliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, Peoples R China, 3College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China, 4University of Chinese Academy of Sciences, Beijing 100049, Peoples R China,5 Department of Cardiology, Tianjin Medical University General Hospital, Tianjin Medial University, Tianjin 300052, China, 6Hunan Co-Innovation Center of Animal Production Safety, CICAPS, Changsha, 410128, Peoples R China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The gene location, tissues distribution of TRPM2
4. The basic structure of TRPM2
5. Variants of TRPM2
6. Activators for TRPM2
7. Inhibitors for TRPM2
8. TRPM2 will be activated during oxidative stress
9. Function and potential application in drug discovery of TRPM2
10. Discussion
11. Acknowledgement
12. References

1. ABSTRACT

The Transient Receptor Potential Melastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel and Adenosine 5’-DiphosPhatase Ribose (ADPR) hydrolase function. TRPM2 is involved in Ca2+ signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+ entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis. The wide expression of TRPM2 might render it as a potentially significant therapeutic target in pathological settings including cardiovascular and neurodegenerative diseases and of great relevance in drug design, feed additives and other industries. Here, we discuss the TRPM2 gene structure, function, its variants, as well as its activators and inhibitors and provide a peptide drug design for modulation of oxidative stress.

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Abbreviations: 2-APB: 2-aminoethoxydiphenyl borate; 6TM: Six trans-membrane; ACA: N- (p-amylcinnamoyl) anthranilic acid; ADPR: Adenosine diphospho-ribose; AMP: adenosine monophosphate; BD: Bipolar disorder; FFA: flufenamic acid; H2O2: hydrogen peroxide; NAD: nicotinamide adenine dinucleotide; NADases: NAD+ glycohydrolases; NUDT9-H: Nucleoside diphosphate linked moiety X-type motif 9 homology; O2: Oxygen; PARP: poly-adenine dinucleotide phosphate-ribose polymerase; ROS: Reactive oxygen species; SNP: single nucleotide polymorphisms; SOD: superoxide dismutase ; SSF-TRPM2: striatum short form transient receptor potential (melastatin) 2; TNFα: tumor necrosis factor α; TRP: The transient receptor potential channel; TRPC7: Transient receptor potential-related channel 7; TRPM2: The transient receptor potential (melastatin) 2; TRPM2-WT:The transient receptor potential (melastatin) 2 wild type.

Key Words: Transient receptor potential melastatin 2, Oxidative stress, Calcium-permeable channel, Drug design, Review

Send correspondence to: Zemeng Feng, Address: Mapoling of Changsha City, Hunan province, P. R. China, Tel: +86-731-84619706, Fax: 86-731-84612685, E-mail: zemengfeng2006@163.com