Peroxisomes as a cellular source of reactive nitrogen species signal molecules

Peroxisomes are single membrane-bounded subcellular organelles with an essentially oxidative type of metabolism and are probably the major sites of intracellular H₂O₂ production. These organelles also generate superoxide radicals () and besides catalase they have a complex battery of antioxidative enzymes. In recent years the existence of l-arginine-dependent nitric oxide synthase (NOS) activity and the generation of the reactive nitrogen species (RNS) nitric oxide (NO) have been demonstrated in plant peroxisomes. The inter-cellular and intracellular NO carrier S-nitrosoglutathione (GSNO) can be generated inside peroxisomes and the presence of this RNS has been demonstrated in peroxisomes from several plant species. This review analyzes the available evidence concerning the properties of the NOS activity and the generation of the RNS messengers NO and GSNO in peroxisomes in the context of the cellular function of these organelles as a source of RNS signaling molecules. The important physiological functions displayed by NO and other RNS in intra- and inter-cellular communication in different organisms indicate that more attention should be payed to the RNS signaling function of peroxisomes in human, animal and fungal cells, where it is very likely that similar mechanisms to those found in plant peroxisomes are also operative.     

Functional role of nitric oxide in plants

The review considers involvement of nitric oxide (NO) in regulation of basic physiological processes underlying growth, development, and senescence in plants. The NO sources in plants, as well as direct and indirect NO signaling mechanisms are also reviewed. Particular attention is paid to the role of this secondary messenger in plant responses to various abiotic stresses, such as mechanical injury, salinity, drought, UV irradiation, high and low temperatures, ozonation, hypoxia, the impacts of heavy metals and herbicides. The role of NO in the hypersensitive response and in a systemic response upon plant infection with invasive pathogens is described.     

Nitric oxide signalling via cytoskeleton in plants

Nitric oxide (NO) in plant cell mediates processes of growth and development starting from seed germination to pollination, as well as biotic and abiotic stress tolerance. However, proper understanding of the molecular mechanisms of NO signalling in plants has just begun to emerge. Accumulated evidence suggests that in eukaryotic cells NO regulates functions of proteins by their post-translational modifications, namely tyrosine nitration and S-nitrosylation. Among the candidates for NO-downstream effectors are cytoskeletal proteins because of their involvement in many processes regulated by NO. This review discusses new insights in plant NO signalling focused mainly on the involvement of cytoskeleton components into NO-cascades. Herein, examples of NO-related post-translational modifications of cytoskeletal proteins, and also indirect NO impact, are discussed. Special attention is paid to plant α-tubulin tyrosine nitration as an emerging topic in plant NO research.     

Mechanisms for nitric oxide synthesis in plants

The discovery that nitric oxide (NO) acts as a signal fundamentally shifted our understanding of free radicals from toxic by-products of oxidative metabolism to key regulators of cellular functions. This discovery has led to intense investigation into the synthesis of NO in both animals and plants. Nitric oxide synthases (NOS) are the primary sources of NO in animals and are complex, highly regulated enzymes that oxidize arginine to NO and citrulline. Plant NO synthesis, however, appears more complex and includes both nitrite and arginine-dependent mechanisms. The components of the arginine pathway have been elusive as no known orthologues of animal NOS exist in plants. An Arabidopsis gene (AtNOS1) has been identified that is needed for NO synthesis in vivo and has biochemical properties similar to animal cNOS, yet it has no sequence similarity to any known animal NOS. An Atnos1 insertion mutant has been useful for genetic studies of NO regulation and for uncovering new roles for NO signalling. The elucidation of plant NO synthesis promises to yield novel mechanisms that may be applicable to animal systems.     

Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation

Nitric oxide (NO), an important cellular messenger, has been linked to both neurodegenerative and neuroprotective actions. In the present review, we focus on recent data establishing a survival and differentiation role for NO in several neural in vitro and in vivo models. Nitric oxide has been found to be essential for survival of neuronal cell lines and primary neurons in culture under various death challenges. Furthermore, its lack may aggravate some neuropathological conditions in experimental animals. Several cellular pathways and signaling systems subserving this neuroprotective role of NO are considered in the review. Survey of recent data related to the developmental role of NO mainly focus on its action as a negative regulator of neuronal precursor cells proliferation and on its role of promotion of neuronal differentiation. Discussion on discrepancies arising from the literature is focused on the Janus-faced properties of the molecule and it is proposed that most controversial results are related to the intrinsic property of NO to compensate among functionally opposed effects. As an example, the increased proliferation of neural cell precursors under conditions of NO shortage may be, later on in the development, compensated by increased elimination through programmed cell death as a consequence of the lack of the survival-promoting action of the molecule. To elucidate these complex, and possibly contrasting, effects of NO is indicated as an important task for future researches.     

The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons

Nitric oxide (NO) affects reproductive processes both at the level of the brain and reproductive tract and this review is focused on its role as an essential regulator of the hypothalamic control of reproduction. The data gathered indicate that glutamate stimulates noradrenergic neurons which subsequently activate NO-ergic cells via alpha1-adrenergic receptors. The released NO diffuses into luteinizing hormone-releasing hormone (LHRH) terminals where it triggers LHRH secretion by activation of guanylyl cyclase and cyclooxygenase. The NO released by estrogen-stimulated NO-ergic ventromedial neurons plays a crucial role in the regulation of sexual behavior. Furthermore, an increased expression of inducible nitric oxide synthase in the LHRH and oxytocin neurons underlies the destructive action of NO on the aging of the hypothalamic neuroendocrine pathways. Within the hypothalamo-hypophyseal system, NO exerts an inhibitory effect in the control of oxytocin secretion. This action seems to employ an indirect mechanism by which NO may modulate the release of GABA. This review provides an overview of the role of NO in hypothalamic control of LHRH and oxytocin release, aging of the LHRH and oxytocin neurons and sexual behavior.     

The effect of different antioxidants on nitric oxide production in hypertensive rats

The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) production appears to be a common feature of experimental and human hypertension. Previously, different antioxidants and/or scavengers of oxygen free radicals were shown to activate nitric oxide synthase (NO synthase, NOS) and to increase the expression of both endothelial and neuronal NO synthase isoforms leading to blood pressure reduction. On the other hand, various antihypertensive drugs have been documented to possess antioxidant properties, which may contribute to their beneficial effect on blood pressure. This review is focused on the effects of antioxidant treatment in different models of experimental hypertension with a special attention to the prevention of oxidative damage and the augmentation of NO synthase activity and expression of NOS isoforms.     

Role of nitric oxide in tolerance of plants to abiotic stress

Nitric oxide (NO) has now gained significant place in plant science, mainly due to its properties (free radical, small size, no charge, short-lived, and highly diffusible across biological membranes) and multifunctional roles in plant growth, development, and regulation of remarkable spectrum of plant cellular mechanisms. In the last few years, the role of NO in tolerance of plants to abiotic stress has established much consideration. As it is evident from the present review, recent progress on NO potentiality in tolerance of plants to environmental stresses has been impressive. These investigations suggest that NO, itself, possesses antioxidant properties and might act as a signal in activating ROS-scavenging enzyme activities under abiotic stress. NO plays an important role in resistance to salt, drought, temperature (high and low), UV-B, and heavy metal stress. Rapidly increasing evidences indicate that NO is essentially involve in several physiological processes; however, there has been much disagreement regarding the mechanism(s) by which NO reduces abiotic stress.     

New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress

Globin-like oxygen-binding proteins occur in bacteria, yeasts and other fungi, and protozoa. The simplest contain protohaem as sole prosthetic group, but show considerable variation in their similarity to the classical animal globins and plant globins. Flavohaemoglobins comprise a haem domain homologous to classical globins and a ferredoxin-NADP+ reductase (FNR)-like domain that converts the globin into an NAD(P)H-oxidizing protein with diverse reductase activities. In Escherichia coli, the prototype flavohaemoglobin (Hmp) is clearly involved in responses to nitric oxide (NO) and nitrosative stress: (i) the structural gene hmp is upregulated by NO and nitrosating agents; (ii) purified Hmp binds NO avidly, but also converts it to nitrate (aerobically) or nitrous oxide (anaerobically); (iii) hmp mutants are hypersensitive to NO and nitrosative stresses. Here, we review recent advances in E. coli and the growing number of microbes in which globins are known, draw particular attention to the essential chemistry of NO and related reactive species and their interactions with globins, and suggest that microbial globins have additional functions unrelated to 'NO' stresses.     

Hydrogen sulfide,a signaling molecule in plant stress responses

Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.     

Role of iNOS in osteoarthritis: Pathological and therapeutic aspects

Accumulating evidence suggests that inflammation has a key role in the pathogenesis of osteoarthritis (OA). Nitric oxide (NO) has been established as one of the major inflammatory mediators in OA and drives many pathological changes during the development and progression of OA. Excessive production of NO in chondrocytes promotes cartilage destruction and cellular injury. The synthesis of NO in chondrocytes is catalyzed by inducible NO synthase (iNOS), which is thereby an attractive therapeutic target for the treatment of OA. A number of direct and indirect iNOS inhibitors, bioactive compounds, and plant-derived small molecules have been shown to exhibit chondroprotective effects by suppressing the expression of iNOS. Many of these iNOS inhibitors hold promise for the development of new, disease-modifying therapies for OA; however, attempts to demonstrate their success in clinical trials are not yet successful. Many plant extracts and plant-derived small molecules have also shown promise in animal models of OA, though further studies are needed in human clinical trials to confirm their therapeutic potential. In this review, we discuss the role of iNOS in OA pathology and the effects of various iNOS inhibitors in OA.     

The roles of NO in microbial symbioses

Because of its unique chemical properties, nitric oxide (NO) is a pluripotent signalling and effector molecule that is implicated in a variety of biological roles. Although NO is known to function in host innate immunity against pathogen invasion, its possible roles in microbial symbioses with animal and plant hosts remain relatively less well defined. In this review, we discuss the mechanisms by which bacteria sense and/or detoxify NO. We then focus specifically on its roles in microbial symbioses of diverse eukaryotic hosts. Using the squid-vibrio light-organ symbiosis as a well-characterized example, we discuss the ways in which NO serves as a signal, antioxidant and specificity determinant in this model symbiosis. Because beneficial microbial associations are older and much more prevalent than pathogenic ones, it seems likely that the former may be evolutionary precursors of the latter. Thus, knowledge of the roles played by NO in mutualisms will provide insights into its function in disease interactions as well.     

Present knowledge and controversies,deficiencies, and misconceptions on nitric oxide synthesis,sensing, and signaling in plants

After 30 years of intensive work, nitric oxide (NO) has just started to be characterized as a relevant regulatory molecule on plant development and responses to stress. Its reactivity as a free radical determines its mode of action as an inducer of posttranslational modifications of key target proteins through cysteine S-nitrosylation and tyrosine nitration. Many of the NO-triggered regulatory actions are exerted in tight coordination with phytohormone signaling. This review not only summarizes and updates the information accumulated on how NO is synthesized, sensed, and transduced in plants but also makes emphasis on controversies, deficiencies, and misconceptions that are hampering our present knowledge on the biology of NO in plants. The development of noninvasive accurate tools for the endogenous NO quantitation as well as the implementation of genetic approaches that overcome misleading pharmacological experiments will be critical for getting significant advances in better knowledge of NO homeostasis and regulatory actions in plants.     

NO way to live; the various roles of nitric oxide in plant-pathogen interactions

Nitric oxide has attracted considerable interest from plant pathologists due its established role in regulating mammalian anti-microbial defences, particularly via programmed cell death (PCD). Although NO plays a major role in plant PCD elicited in response to certain types of pathogenic challenge, the race-specific hypersensitive response (HR), it is now evident that NO also acts in the regulation of non-specific, papilla-based resistance to penetration by plant cells that survive attack and, possibly, in systemic acquired resistance. Equally, the potential roles of NO signalling/scavenging within the pathogen are being recognized. This review will consider key defensive roles played by NO in living cells during plant-pathogen interactions, as well as in those undergoing PCD.     

Integrative response of plant mitochondrial electron transport chain to nitrogen source

Nitrogen (N) availability is widely known as a determinant of plant growth and respiration rate. However, less attention has been paid to the effect of the type of N source (nitrate, nitrite or ammonium) on the respiratory system. This review summarizes the latest findings on this topic, with an emphasis on the effect of ammonium and nitric oxide (NO) on the respiratory system, and the physiological role of alternative oxidase (AOX). First, concentrated ammonium has been found to increase plant respiration rate (ammonium-dependent respiratory increase, ARI). We will introduce two hypotheses to explain ARI, futile ammonium cycling and excess reducing equivalents, and verify the validity of each hypothesis. We suggest that these two hypotheses are not necessarily mutually exclusive. Second, gene expression of AOX is suppressed when N is predominately available as nitrate instead of ammonium. We will discuss possible signaling pathways leading to this expression pattern. Third, while AOX expression is induced by NO, AOX activity itself is insensitive to NO. In contrast, activity of cytochrome c oxidase (COX) is sensitive to NO. We outline the NO production pathway, focusing on nitrite-dependent NO production, and discuss the physiological significance of the fact that AOX activity is insensitive to NO. Finally, this review aims to build an integrated scheme of the respiratory response to the type of N source, considering leaves in high light conditions or hypoxic roots.     

The nitric oxide pathway in the cardiovascular system

The present review analyzes the role nitric oxide (NO) plays in the homeostasis of the cardiovascular system. By regulating vascular smooth muscle cell and myocyte contractility, myocardial oxygen consumption and renal tubular transport, this simple molecule plays a central role in the control of vascular tone, cardiac contractility and short and long term regulation of arterial pressure. Fifteen years ago, all we knew about NO is that it had very similar properties as those of endothelium-derived relaxing factor and that its action was probably mediated by cGMP. An enormous amount of knowledge has since been amassed on the biochemical pathways that NO follows from the moment it is synthesized from L-arginine until the physiological or pathological actions take place in the effector cells. This review intends to organize this knowledge in a fashion that is easy to understand. We will dissect the NO pathway in different steps, focusing on the physiological and pathophysiological actions of the isoenzymes which synthesize NO, the molecules involved in this synthesis such as caveolins, protein kinases and cofactors, the situations in which endogenous inhibitors of NO synthase are formed from L-arginine instead of NO, the way in which NO exerts its physiological actions through cGMP-dependent protein kinases and finally, the pathological routes NO may follow when the oxidative status of the cell is high.     

亚硝基化在植物细胞死亡及防御反应中的作用

亚硝基化是近年来新发现的不依赖于环磷酸鸟苷的一氧化氮信号转导途径, 是一氧化氮分子通过共价结合修饰靶蛋白的半胱氨酸残基从而改变其功能的过程。该文重点综述了近年来亚硝基化在细胞死亡和抗病反应这两个紧密关联的生物学过程中的最新研究成果, 总结了亚硝基化通过修饰和调控靶蛋白从而促进或抑制细胞死亡和抗病反应, 并对现有研究结果中某些不一致之处提出自己的观点。最后根据动物学领域的最新研究进展对植物学领域未来亚硝基化的研究方向进行了展望。