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Hypothermia translocates nitric oxide synthase from cytosol to membrane in snail neurons

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Abstract

Neuronal nitric oxide (NO) levels are modulated through the control of catalytic activity of NO synthase (NOS). Although signals limiting excess NO synthesis are being extensively studied in the vertebrate nervous system, our knowledge is rather limited on the control of NOS in neurons of invertebrates. We have previously reported a transient inactivation of NOS in hibernating snails. In the present study, we aimed to understand the mechanism leading to blocked NO production during hypothermic periods of Helix pomatia. We have found that hypothermic challenge translocated NOS from the cytosol to the perinuclear endoplasmic reticulum, and that this cytosol to membrane trafficking was essential for inhibition of NO synthesis. Cold stress also downregulated NOS mRNA levels in snail neurons, although the amount of NOS protein remained unaffected in response to hypothermia. Our studies with cultured neurons and glia cells revealed that glia–neuron signaling may inhibit membrane binding and inactivation of NOS. We provide evidence that hypothermia keeps NO synthesis “hibernated” through subcellular redistribution of NOS.

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Abbreviations

BH4:

Tetrahydrobiopterin

CNS:

Central nervous system (cerebral and subesophageal ganglia)

CYTRI :

Relative intensity of cytoplasmic NADPHd staining

DIC:

Differential interference contrast

DXM:

Dexamethasone

FMN:

Flavin mononucleotide

FrK:

Forskolin

FAD:

Flavin adenin dinucleotide

HelixNOS:

Helix pomatia neuronal NOS

NMDA:

N-methyl-D-aspartate

NADPH:

Reduced nicotinamide-dinucleotide-phosphate

NADPHd:

NADPH diaphorase

NOS:

Nitric oxide synthase

PNRRI :

Relative intensity of perinuclear NADPHd staining

QRC:

Quercetin

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Acknowledgements

We are grateful to Dr. Lucía Fuentes and Dr. Christian Hellriegel for valuable discussion.

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  1. Tamás Rőszer

    Present address: Department of Regenerative Cardiology, Spanish National Cardiovascular Research Center, 28029, Madrid, Melchor Fernandez Almagro 3, Spain

Authors and Affiliations

  1. Department of Microbial Biotechnology and Cell Biology (formerly Animal Anatomy and Physiology), Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary

    Tamás Rőszer, Éva Kiss-Tóth, Dávid Rózsa & Gáspár Bánfalvi

  2. Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Tamás Józsa

  3. Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    A. József Szentmiklósi

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Rőszer, T., Kiss-Tóth, É., Rózsa, D. et al. Hypothermia translocates nitric oxide synthase from cytosol to membrane in snail neurons. Cell Tissue Res 342, 191–203 (2010). https://doi.org/10.1007/s00441-010-1063-8

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