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New Molecular Mechanisms on the Activation of TRPM2 Channels by Oxidative Stress and ADP-Ribose

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Abstract

The Na+ and Ca2+-permeable melastatin related transient receptor potential (TRPM2) cation channels can be gated either by ADP-ribose (ADPR) in concert with Ca2+ or by hydrogen peroxide (H2O2), an experimental model for oxidative stress, and binding to the channel’s enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 inhibiting in response to ADPR and H2O2 are not understood, I reviewed the effects of various inhibitors such as flufenamic acid and PARP inhibitors on ADPR, NAD+ and H2O2-induced TRPM2 currents. In our experimental study, TRPM2 cation channels in chinese hamster ovary transected cells were gated both by ADPR and NAD+. In addition, H2O2 seems to activate TRPM2 by changing to the hydroxyl radical in the intracellular space after passing the plasma membrane. Experimental studies with respect to patch-clamp and Ca2+ imaging, inhibitor roles of antioxidants are also summarized in the review.

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Abbreviations

ADPR:

Adenosine diphosphatase ribose

ANT:

Adenine nucleotide translocases

CHO:

Chinese hamster ovary

CRG-G1:

Cambridge rat insulinoma G1

DAG:

Diacyl glycerol

DMTU:

Dimethylthiourea;

DP:

2,2’-Dipyridyl

eNOS:

Endothelial nitric oxide synthase

FFA:

Flufenamic acid

GR:

Glutathione reductases

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

GSSG:

Oxidized glutathione

HEK:

Human embryonic kidney

MPG:

2-Mercaptopropionylglycine

NMDG:

N-methyl-d-glucamine

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PARG:

Poly(ADP-ribose) glycohydrolase

PARP-1:

Poly(ADP-ribose) polymerase

PTP:

Permeability transition pores

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TRP:

Transient receptor potential

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Acknowledgment

The author thanks to Dr. Jim W. Jr Putney on comments of the manuscript in National Institute of Environmental Health Sciences, NIH, NC, USA.

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  1. Department of Biophysics, Medical (TIP) Faculty, Süleyman Demirel University, 32260, Cunur, Isparta, Turkey

    Mustafa Nazıroğlu

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Nazıroğlu, M. New Molecular Mechanisms on the Activation of TRPM2 Channels by Oxidative Stress and ADP-Ribose. Neurochem Res 32, 1990–2001 (2007). https://doi.org/10.1007/s11064-007-9386-x

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