Hemoglobin-mediated nitric oxide signaling

The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the dioxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitrosothiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered.     

Adaptive evolution of larvae and life cycles

The larval patterns of marine invertebrates pose intriguing questions for both evolutionary and developmental biologists. However, combined investigations have been rare. Quantitative models analyze the selective factors that drive evolutionary change in larval nutrition and timing of metamorphosis. Developmental studies describe the morphogenesis characterizing ancestral and derived larval patterns. Rigorous evolutionary analysis of the transition to derived modes of development is lacking and detailed developmental and ecological data are needed to test and refine theoretical models. A major challenge facing studies of life cycle evolution is the elucidation of the genetic structure and covariance of important developmental and larval traits.     

Origin and evolution of animal life cycles

The ‘origin of larvae’ has been widely discussed over the years, almost invariably with the tacit understanding that larvae are secondary specializations of early stages in a holobenthic life cycle. Considerations of the origin and early radiation of the metazoan phyla have led to the conclusion that the ancestral animal (= metazoan) was a holopelagic organism, and that pelago-benthic life cycles evolved when adult stages of holopelagic ancestors became benthic, thereby changing their life style, including their feeding biology. The literature on the larval development and phylogeny of animal phyla is reviewed in an attempt to infer the ancestral life cycles of the major animal groups. The quite detailed understanding of larval evolution in some echinoderms indicates that ciliary filter-feeding was ancestral within the phylum, and that planktotrophy has been lost in many clades. Similarly, recent studies of the developmental biology of ascidians have demonstrated that a larval structure, such as the tail of the tadpole larva, can easily be lost, viz. through a change in only one gene. Conversely, the evolution of complex structures, such as the ciliary bands of trochophore larvae, must involve numerous genes and numerous adaptations. The following steps of early metazoan evolution have been inferred from the review. The holopelagic ancestor, blastaea, probably consisted mainly of choanocytes, which were the feeding organs of the organism. Sponges may have evolved when blastaea-like organisms settled and became reorganized with the choanocytes in collar chambers. The eumetazoan ancestor was probably the gastraea, as suggested previously by Haeckel. It was holopelagic and digestion of captured particles took place in the archenteron. Cnidarians and ctenophores are living representatives of this type of organization. The cnidarians have become pelago-benthic with the addition of a sessile, adult polyp stage; the pelagic gastraea-like planula larva is retained in almost all major groups, but only anthozoans have feeding larvae. Within the Bilateria, two major lines of evolution can be recognized: Protostomia and Deuterostomia. In protostomes, trochophores or similar types are found in most spiralian phyla; trochophore-like ciliary bands are found in some rotifers, whereas all other aschelminths lack ciliated larvae. It seems probable that the trochophore was the larval type of the ancestral, pelago-benthic spiralian and possible that it was ancestral in all protostomes. Most of the non-chordate deuterostome phyla have ciliary filter-feeding larvae of the dipleurula type, and this strongly indicates that the ancestral deuterostome had this type of larva.     

Phylogeny of Medusozoa and the evolution of cnidarian life cycles

To investigate the evolution of cnidarian life cycles, data from the small subunit of the ribosome are used to derive a phylogenetic hypothesis for Medusozoa. These data indicate that Cnidaria is monophyletic and composed of Anthozoa and Medusozoa. While Cubozoa and Hydrozoa are well supported clades, Scyphozoa appears to be paraphyletic. Stauromedusae is possibly the sister group of either Cubozoa or all other medusozoans. The phylogenetic results suggest that: the polyp probably preceded the medusa in the evolution of Cnidaria; within Hydrozoa, medusa development involving the entocodon is ancestral; within Trachylina, the polyp was lost and subsequently regained in the parasitic narcomedusans; within Siphonophorae, the float originated prior to swimming bells; stauromedusans are not likely to be descended from ancestors that produced medusae by strobilation; and cubozoan polyps are simplified from those of their ancestors, which possessed polyps with gastric septa and four mesogleal muscle bands and peristomial pits.     

Responses of the haploid-to-diploid ratio of isomorphic biphasic life cycles to time instability

Previous modelling of the haploid-to-diploid ratio (H:D) in biphasic life cycles relied on estimates of the stable population growth rate and structure. This is a projective analysis that estimates the population dynamics given current conditions. However, the environment is rarely constant and has both periodicity and random instabilities. The objective of this work was to unveil how the H:D responds to them. It was found that ploidy phase dissimilarities on the demographic matrix and/or in the initial population structure cause an inevitable H:D time variability as a consequence of the life-cycle structure and independent of the environmental seasonal cycle. This variability depends on the type of life strategy, demographic processes involved and ploidy dissimilar vital rates. Furthermore, ploidy dissimilar fertility or growth rates cause cyclic oscillations mismatching the seasonal cycle, whereas ploidy dissimilarities in the ramet looping rates (survival related) induce a monotonical variation.     

Effects of nitric oxide on proprioceptive signaling

We have analysed the effects of the neuromodulator nitric oxide (NO) on proprioceptive information processing by ascending intersegmental interneurons that form part of the local circuits within the terminal abdominal ganglion of the crayfish. NO modulates the synaptic inputs to ascending interneurons, enhancing the amplitude of class I interneurons and reducing the amplitude of class II interneurons. Repetitive proprioceptive stimulation leads to rapid depression in a specific set of identified interneurons but not in others. Bath application of a nitric oxide scavenger, PTIO, causes a significant decrease in the rate of depression of the interneurons showing a rapid depression, independent of interneuron class, but has no effect on the dynamic responses of the interneurons that show little initial depression. These results indicate that NO exerts multiple effects at the very first stage of synaptic integration in local circuits.     

Regulatory roles of nitric oxide during larval development and metamorphosis in Ciona intestinalis

Metamorphosis in the ascidian Ciona intestinalis is a very complex process which converts a swimming tadpole to an adult. The process involves reorganisation of the body plan and a remarkable regression of the tail, which is controlled by caspase-dependent apoptosis. However, the endogenous signals triggering apoptosis and metamorphosis are little explored. Herein, we report evidence that nitric oxide (NO) regulates tail regression in a dose-dependent manner, acting on caspase-dependent apoptosis. An increase or decrease of NO levels resulted in a delay or acceleration of tail resorption, without affecting subsequent juvenile development. A similar hastening effect was induced by suppression of cGMP-dependent NO signalling. Inhibition of NO production resulted in an increase in caspase-3-like activity with respect to untreated larvae. Detection of endogenously activated caspase-3 and NO revealed the existence of a spatial correlation between the diminution of the NO signal and caspase-3 activation during the last phases of tail regression. Real-time PCR during development, from early larva to early juveniles, showed that during all stages examined, NO synthase (NOS) is always more expressed than arginase and it reaches the maximum value at late larva, the stage immediately preceding tail resorption. The spatial expression pattern of NOS is very dynamic, moving rapidly along the body in very few hours, from the anterior part of the trunk to central nervous system (CNS), tail and new forming juvenile digestive organs. NO detection revealed free diffusion from the production sites to other cellular districts. Overall, the results of this study provide a new important link between NO signalling and apoptosis during metamorphosis in C. intestinalis and hint at novel roles for the NO signalling system in other developmental and metamorphosis-related events preceding and following tail resorption.     

On the origins of nitric oxide

Nitric oxide (NO) is widely recognized for its role as signaling compound. However, the metabolic mechanisms that determine changes in the level of NO in plants are only poorly understood, despite this knowledge being crucial to understanding the signal function of NO. To date, at least seven possible pathways of NO biosynthesis have been described for plants, although the molecular and enzymatic components are resolved for only one of these. Currently, this represents the most significant bottleneck for NO research. In this review, we provide an overview of the multiplicity of NO production and scavenging pathways in plants. Furthermore, we discuss which areas should be focused on in future studies to investigate the origin of fluctuations in the level of NO in plants.     

Extracellular nitric oxide signaling in the hamster biological clock

Nocturnal light pulses induce phase shifts in circadian rhythms and activate cFos expression in the suprachiasmatic nuclei (SCN). We have studied the role of nitric oxide (NO) in the intercellular communication within the dorsal and ventral portions of the SCN in Syrian hamsters. Administration of the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide blocked photic phase advances in a dose-dependent manner and inhibited light-induced cFos-ir, without affecting light-induced circadian phase delays. These results suggest that NO may act as an intercellular messenger in the SCN, mediating light-induced phase advances.     

The evolution of lamprey (Petromyzontida) life history and the origin of metamorphosis

Modern lampreys (Petromyzontiformes) are one of two lineages of surviving jawless fishes (agnathans), and are thus of critical importance to understanding the evolution of the vertebrates. Although their fossil record is meager, it appears they have remained morphologically conserved for at least 360 million years, but the origin of their multi-stage life history is unclear. Unlike hagfishes, the other extant group of jawless fishes, which exhibit direct development, all modern lampreys possess a complex life cycle which includes a long-lived freshwater larval (or ammocoete) period, followed by a true metamorphosis into a sexually-immature juvenile and then mature adult which differ dramatically in their morphology and ecology from the larva. Because of their basal position, it is critical to understand when the extant lamprey life history evolved, and if such a life history was present in the last common ancestor of agnathans and gnathostomes. Recent discoveries in paleontology, genomic analyses, and developmental biology are providing insights into this problem. The current review synthesizes these findings and concludes that the ancestral lamprey life cycle followed a direct development. We suggest that the larval period was short and relatively limited if present at all, but that the juvenile included modern larval traits; over the course of evolution, differential selection pressures throughout the lifetime produced distinct larval and juvenile/adult periods. Each period required the dramatically different morphologies seen in modern lampreys, ultimately requiring a true metamorphosis to accommodate the large changes in the body plan and to maximize the efficiency of each life period. As a result, modern lamprey life histories are a patchwork of ancestral and derived characters.     

The evolution of life cycles with haploid and diploid phases

Sexual eukaryotic organisms are characterized by an alternation between haploid and diploid phases. In vascular plants and animals, somatic growth and development occur primarily in the diploid phase, with the haploid phase reduced to the gametic cells. In many other eukaryotes, however, growth and development occur in both phases, with substantial variability among organisms in the length of each phase of the life cycle. A number of theoretical models and experimental studies have shed light on factors that may influence life cycle evolution, yet we remain far from a complete understanding of the diversity of life cycles observed in nature. In this paper we review the current state of knowledge in this field, and touch upon the many questions that remain unanswered. BioEssays 20 :453–462, 1998. © 1998 John Wiley & Sons, Inc.     

Relationships among development, ecology, and morphology in the evolution of Echinoderm larvae and life cycles

The evolution of life cycles involves transitions between discrete states in one or more of the characters that comprise a developmental pattern. In this paper, we examine three of the major life cycle characters and the states for these characters. Using examples from echinoderms, we discuss the evolutionary transitions that have occurred in the type of morphogenesis, developmental habitat, and mode of nutrition during development. We evaluate the functional requirements associated with these transitions to infer the likelihood (frequency or rapidity) of change in a given character and of biases in the polarity of character state transitions. Using comparisons of closely related species, we evaluate the change between states in one character for dependence on the state of, or correlated changes in, other characters. Based on our analysis of congeneric species that differ in developmental habitat, we conclude that the transition between pelagic and benthic development is an ecological change that is independent of changes in morphogenesis and should be reversible. In contrast, the transition from feeding to nonfeeding development has been considered to be irreversible because it involves marked changes in larval morphology. We re-examine the transition between different modes of larval nutrition in light of recent studies that show that there exists a continuum of nutritional strategies between planktotrophy and lecithotrophy. This continuum is largely determined by variation in maternal investment and does not involve alterations in larval morphology. We suggest that the boundary between planktotrophy and lecithotrophy is frequently crossed and that this transition is reversible. Ecological changes represent the crossing of a functional threshold. Only after crossing the threshold, do larvae experience qualitatively different selective pressures that can lead to subsequent changes in morphology and development. Two different changes have occurred in the type of morphogenesis: the simplification of larval morphology that is associated with obligate (nonfeeding) lecithotrophy and the loss of the larval body plan in the evolution from indirect to direct development. It is the modification of morphology independent of the ecological changes that requires alterations in developmental processes, constrains evolutionary options, imposes irreversibility, and establishes the discrete nature of larval patterns in marine invertebrates.     

Mitochondrial nitric oxide in the signaling of cell integrated responses

Mitochondria are the specialized organelles for energy metabolism, but, as a typical example of system biology, they also activate a multiplicity of pathways that modulate cell proliferation and mitochondrial biogenesis or oppositely promote cell arrest and programmed cell death by a limited number of oxidative or nitrosative reactions. These reactions are influenced by matrix nitric oxide (NO) steady-state concentration, either from local production or by gas diffusion to mitochondria from the canonical sources. Likewise, in a range of 30–200 nM, NO turns mitochondrial O₂ utilization down by binding to cytochrome oxidase and elicits a burst of superoxide anion and hydrogen peroxide that diffuses outside mitochondria. Depending on NO levels and antioxidant defenses, more or less H₂O₂ accumulates in cytosol and nucleus, and the resulting redox grading contributes to dual activation of proliferating and proapoptotic cascades, like ERK1/2 or p38 MAPK. Moreover, these sequential activating pathways participate in rat liver and brain development and in thyroid modulation of mitochondrial metabolism and contribute to hypothyroid phenotype through complex I nitration. On the contrary, lack of NO disrupts pathways like S-nitrosylation or H₂O₂ production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation. peroxynitrite; hydrogen peroxide; mitochondrial nitric oxide synthase; mitogen-activated protein kinase     

Role of nitric oxide dependence on nitric oxide synthase-like activity in the water stress signaling of maize seedling

Nitric oxide (NO) has been known as an important signal in plant antioxidative defense but its production and roles in water stress are less known. The present study investigated whether NO dependence on a NO synthase-lika (NOS) activity is involved in the signaling of drought-induced protective responses in maize seedlings. NOS activity, rate of NO release and drought responses were analyzed when NO donor sodium nitroprusside (SNP), NO scavenger c-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramathylimidazoline-1-oxyl-3-oxide) and NOS inhibitor L-NAME (NG-nitro-L-arginine methyl ester) were applied to both detached maize leaves and whole plants. Both NOS activity and the rate of NO release increased substantially under dehydration stress. The high NOS activity induced by c-PTIO as NO scavenger and NO accumulation Inhibited by NOS inhibitor L-NAME In dehydration-treated maize seedlings Indicated that most NO production under water deficit stress may be generated from NOS-like activity. After dehydration stress for 3 h, detached maize leaves pretreated with NO donor SNP maintained more water content than that of control leaves pretreated with water. This result was consistent with the decrease in the transpiration rate of SNP-treated leaves subjected to drought treatment for 3 h. Membrane permeability, a cell injury index, was lower in SNP-trested maize leaves under dehydration stress for 4 h when compared with the control leaves. Also, superoxide dismutsse (SOD) activity of SNP combined drought treatment maize leaves was higher than that of drought treatment alone, indicating that exogenous NO treatment alleviated the water loss and oxidative damage of maize leaves under water deficit stress. When c-PTIO as a specific NO scavenger was applied, the effects of applied SNP were overridden. Treatment with L-NAME on leaves also led to higher membrane permeability, higher transpiration rate and lower SOD activities than those of control leaves, indicating that NOS-like activity was involved in the antioxidative defense under water stress. These results suggested that NO dependence on NOS-like activity serves as a signaling component in the induction of protective responses and is associated with drought tolerance in maize seedlings.     

The early role of nitric oxide in evolution

Nitric oxide (NO), which today serves many different purposes in regulating complex cellular functions, must have played a crucial role in the early stages of the evolution of life. The formation of NO may have been a critical defence mechanism for primitive microorganisms at a time when life faced the problem of rising atmospheric levels of ozone (03) formed upon photolysis of oxygen (Oz), which occurred shortly after the development of respiration in cyanobacteria. The production of NO by organisms would have allowed neutralization of toxic 03 by chemical reaction outside the cell, thus acting as a protective mechanism against oxidative destruction, allowing evolutionary advantage. Later, NO production might have allowed the control of reactive OZ species within cells before the development of specific electron-accepting enzymes. The pathway of NO formation was then consequently developed further to serve other useful functions. Although mammalian cells produce NO from L-arginine, the origin of this ability might have arisen from the essential process of either nitrification or denitrification in prokaryotic cells.     

Molecular evolution of nitric oxide synthases in metazoans

Nitric oxide synthases (NOS), the enzymes responsible for the NO synthesis, are present in all eukaryotes. Three isoforms (neuronal, inducible and endothelial), encoded by different loci, have been described in vertebrates, although the endothelial isoform seems to be restricted to tetrapods. In invertebrates, a variety of NOS isoforms have been variably annotated as "inducible" or "neuronal", while others lack precise annotation. We have performed an exhaustive collection of the available NOS amino-acid sequences in order to perform a phylogenetic analysis. We hypothesized that the NOS isoforms reported in vertebrates derive from 1) different invertebrate NOS, 2) a single invertebrate ancestral gene, through an event related to the double whole genomic duplication that occurred at the origin of vertebrates, and 3) the endothelial form of NOS appeared late in the evolution of vertebrates, after the split of tetrapods and fishes. Our molecular evolution analysis strongly supports the second scenario, the three vertebrate NOS isoforms derived from a single ancestral invertebrate gene. Thus, the diverse NOS isoforms in invertebrates can be explained by events of gene duplication, but their characterization as "inducible" or "neuronal" should only be justified by physiological features, since they are evolutionarily unrelated to the homonym isoforms of vertebrates.