[19 Cysteine Nitric Oxide Interaction and Olfactory Function

By Marie-Christine Broillet

Introduction

The transfer of a nitric oxide group to cysteine sulfhydryls on proteins, known as S-nitrosylation (Fig. 1), is becoming more and more recognized as a ubiquitous regulatory reaction comparable to phosphorylation. It represents a form of redox modulation in diverse tissues including the brain. An increasing number of proteins have been found to undergo S-nitrosylation in vivo.1 These proteins are called S-nitrosothiols. The S-nitrosothiol proteins may play an important role in many processes ranging from signal transduction, DNA repair, host defense, and blood pressure control to ion channel regulation and neurotransmission.

A number of ion channels have been reported to be directly NO sensitive, among them the A'-methyl-D-aspartatc (NMDA) receptor-channel complex,2 Ca2+-activated K+ channels,3 Na+ channels in baroreceptors,4 cardiac Ca2+ release channels,5 L-type Ca2+ channels,6 and our own work on cyclic nucleotide-gated (CNG) channels.7 However, in only a few cases have the specific cysteine residues been determined.8'9 Only the CNG channels have been shown to be opened by S-nitrosylation; in other ion channels, it appears rather that the activation and inactivation parameters are being altered.

1 M.-C. Broillet, Cell. Mol. Life Sci. 55, 1036 (1999).

2 Y.-B. Choi, L. Tenneti, D. A. Le, J. Ortiz, G. Bai, H.-S. V. Chien, and S. A. Lipton, Nat. Neurosci. 3,15 (2000).

3 V. M. Bolotina, S. Najibi, J. Palacino, R Pagano, and R. A. Cohen, Nature (London) 368, 850 (1994).

4 Z. Li, M. W. Chapleau, J. N. Bates, K. Bielefeldt, H.-C. Lee, and F. M. Abboud, Neuron 20, 1039 (1998).

5 L. Xu, J. P. Eu, G. Meissner, and J. S. Stamler, Science 279, 234 (1998).

6 d. C. Campbell, j. S. Stamler, and h. C. Strauss, J. Gen. Physiol. 108, 111 (1996).

7 M.-C. Broillet and S. Firestein, Neuron 16, 377 (1996).

8 J. S. Stamler, L. Jia, J. P. Eu, T. J. McMahon, I. T. Demchenko, J. Bonaventura, K. Gemert, and C. A. Piantadosi, Science 276, 2034 (1997).

9 M.-C. Broillet, J. Biol. Chem. 275, 15135 (2000).

Acknowledgments

Our work in this area is supported by the NIH (ROl HL58248) and through the support of a Marine/Freshwater Biomedical Center Grant (ESO-19Q8) funded by the NIEHS.

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