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Review
. 2023 Jul 6;24(13):11182.
doi: 10.3390/ijms241311182.

Nitric Oxide Function and Nitric Oxide Synthase Evolution in Aquatic Chordates

Annamaria Locascio  1 , Giovanni Annona  1   2 , Filomena Caccavale  1 , Salvatore D'Aniello  1 , Claudio Agnisola  3 , Anna Palumbo  1
Affiliations
Review

Nitric Oxide Function and Nitric Oxide Synthase Evolution in Aquatic Chordates

Annamaria Locascio et al. Int J Mol Sci. .

Abstract

Nitric oxide (NO) is a key signaling molecule in almost all organisms and is active in a variety of physiological and pathological processes. Our understanding of the peculiarities and functions of this simple gas has increased considerably by extending studies to non-mammal vertebrates and invertebrates. In this review, we report the nitric oxide synthase (Nos) genes so far characterized in chordates and provide an extensive, detailed, and comparative analysis of the function of NO in the aquatic chordates tunicates, cephalochordates, teleost fishes, and amphibians. This comprehensive set of data adds new elements to our understanding of Nos evolution, from the single gene commonly found in invertebrates to the three genes present in vertebrates.

Keywords: amphibian; embryonic development; fish; invertebrate chordates; metamorphosis; nervous system.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic resuming of all major transformations putatively involved in nitric oxide (NO) homeostasis. Under normoxic conditions, NO is synthesized by Nos enzymes from L-arginine. In organisms possessing the ornithine–urea cycle (OUC), the co-product of the reaction, L-citrulline, is reconverted to L-arginine (the citrulline–NO cycle). NO signaling may occur by (i) forming an iron-nitrosyl complex with hemoproteins; (ii) promoting protein post-translational modifications via S-nitrosylation, forming S-nitroso compounds with thiol residues (SNO); and (iii) forming N-nitroso (NNO) compounds. NO can be (i) rapidly converted to nitrite with dissolved O2 by NO scavenging reactions or can be (ii) inactivated to nitrate by oxygenated heme proteins. Excess NO (iii) can react with superoxide to form peroxynitrite (ONOO−), which in turn can interact with lipids, DNA, and proteins to give nitrated derivatives or (iv) react with oxygen to form N2O3, which interacts with thiol groups to give nitrosylated proteins. When de novo production via Nos is compromised under low O2, NO can be produced by nitrite reduction in heme proteins (the globin–NO cycle), possibly associated with nitrate conversion to nitrite by xanthine oxidoreductase. The interactions with arginine and protein homeostasis may be significant in determining the balance between NO formation and scavenging.
Figure 2
Figure 2
Nos repertoire in deuterostomes. Silhouettes are from PhyloPic (PhyloPic—free silhouette images of life forms) and represent the following: (1) Human (Homo sapiens); (2) Frog (Xenopus laevis and Xenopus tropicalis); (3) Chicken (Gallus gallus); (4) Lizard (Anolis carolinensis); (5) Coelacanth (Latimeria chalumnae); (6) Medaka (Oryzias latipes); (7) Carp (Carassius auratus, Cyprinus carpio, and Sinocyclocheilus anshuiensis); (8) Zebrafish (Danio rerio); (9) Northern pike (Esox lucius); (10) Salmon (Oncorhynchus mykiss and Salmo salar); (11) Elephant fish (Paramormyrops kingsleyae); (12) Spotted gar (Lepisosteus oculatus); (13) Bowfin (Amia calva); (14) Sturgeon (Acipenser ruthenus); (15) Bichir (Polypterus senegalus); (16) Shark (Scyliorhinus torazame); (17) Lamprey (Lethenteron camtschaticum, Petromyzon marinus); (18) Sea squirt (Ciona robusta and Ciona savignyi); (19) Amphioxus (Asymmetron lucayanum, Branchiostoma belcheri, Branchiostoma floridae, and Branchiostoma lanceolatum); (20) Sea urchin (Hemicentrotus pulcherrimus and Strongylocentrotus purpuratus). Abbreviations: Cs4R, carp-specific genome duplication; Ss4R, salmonid-specific genome duplication; TGD, teleost genome duplication; VGD, vertebrate genome duplication.
Figure 3
Figure 3
Comparison of the major physiological functions of NO in aquatic chordates. The NO roles in immunity, reproduction, feeding and gut function, neuro-modulation, and development are common to all chordates (green). The role in locomotion is conserved among vertebrates and tunicates (lilac), but no data are available in cephalochordates (question mark). NO function in metamorphosis is common to all chordates with an indirect development (light brown). Cardio-respiratory modulation by NO is reported in vertebrates and tunicates (orange).
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References

    1. Hansen M.N., Jensen F.B. Nitric Oxide Metabolites in Goldfish under Normoxic and Hypoxic Conditions. J. Exp. Biol. 2010;213:3593–3602. doi: 10.1242/jeb.048140. - DOI - PubMed
    1. Moroz L.L., Romanova D.Y., Nikitin M.A., Sohn D., Kohn A.B., Neveu E., Varoqueaux F., Fasshauer D. The Diversification and Lineage-Specific Expansion of Nitric Oxide Signaling in Placozoa: Insights in the Evolution of Gaseous Transmission. Sci. Rep. 2020;10:13020. doi: 10.1038/s41598-020-69851-w. - DOI - PMC - PubMed
    1. Shepherd M., Giordano D., Verde C., Poole R.K. The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications. Antioxidants. 2022;11:1222. doi: 10.3390/antiox11071222. - DOI - PMC - PubMed
    1. Hirst D.G., Robson T. Nitric Oxide Physiology and Pathology. Methods Mol. Biol. 2011;704:1–13. doi: 10.1007/978-1-61737-964-2_1. - DOI - PubMed
    1. Locascio A., Vassalli Q.A., Castellano I., Palumbo A. Novel Insights on Nitric Oxide Synthase and NO Signaling in Ascidian Metamorphosis. Int. J. Mol. Sci. 2022;23:3505. doi: 10.3390/ijms23073505. - DOI - PMC - PubMed

Grants and funding

G.A. and F.C. were supported by MUR CIR_0029 Human Capital.

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