植物次生代谢研究

次生代谢是植物重要的生命活动,与植物的生长发育及其对环境的适应密切相关。同时次生代谢产物也是重要的药物和化工原料来源。次生代谢过程及代谢物的积累受到自身和环境中各种生物和非生物因素的调控。随着基因组和代谢组等组学技术的产生和发展,植物次生代谢研究获得了前所未有的机会。通过对代谢过程的深入了解,利用系统生物学方法开展预见性代谢工程将会成为未来的研究趋势。     

Dual action of the active oxygen species during plant stress responses

Adaptation to environmental changes is crucial for plant growth and survival. However, the molecular and biochemical mechanisms of adaptation are still poorly understood and the signaling pathways involved remain elusive. Active oxygen species (AOS) have been proposed as a central component of plant adaptation to both biotic and abiotic stresses. Under such conditions, AOS may play two very different roles: exacerbating damage or signaling the activation of defense responses. Such a dual function was first described in pathogenesis but has also recently been demonstrated during several abiotic stress responses. To allow for these different roles, cellular levels of AOS must be tightly controlled. The numerous AOS sources and a complex system of oxidant scavengers provide the flexibility necessary for these functions. This review discusses the dual action of AOS during plant stress responses.     

Experimental design and reporting standards for metabolomics studies of mammalian cell lines

Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important.     

Reprogramming the metabolome rescues retinal degeneration

Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes—including but not limited to glucose and oxygen metabolism—that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.     

Bacterial suicide through stress

Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially, the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response also has major implications for current [food] processing methods. Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999     

MAP kinases in plant signal transduction

Mitogen-activated protein kinase (MAPK) pathways are modules involved in the transduction of extracellular signals to intracellular targets in all eukaryotes. Distinct MAPK pathways are regulated by different extracellular stimuli and are implicated in a wide variety of biological processes. In plants there is evidence for MAPKs playing a role in the signaling of abiotic stresses, pathogens and plant hormones. The large number and divergence of plant MAPKs indicates that this ancient mechanism of bioinformatics is extensively used in plants and may provide a new molecular handle on old questions.     

Rapid development and a long life: an association expected under a stress theory of aging

Life span and development time are considered in the context of the abiotic stresses to which free-living organisms are normally exposed. Under these circumstances, long life span depends upon metabolically efficient stress-resistance genes, which tend to be heterozygous. Similarly, rapid development time tends to be a feature of heterozygous stress-resistant individuals. Therefore, individuals who have high inherited stress resistance should develop fastest and live longest; in addition, they should show high homeostasis in the face of the energy costs of stress. In this way, the stress theory of aging can incorporate the developmental stage, based upon oxidative stress as an important major direct challenge.     

Life without oxygen: what can and what cannot?

The basic principles involved in the biotransformation of organic carbon compounds in the absence of molecular oxygen (dioxygen) are presented in this paper. The role of various electron acceptors during the breakdown of organic compounds is discussed and the metabolic end-products expected are summarized. The different biochemical possibilities and strategies for the anaerobic degradation of organic matter and the metabolic response of some organisms to anaerobiosis are elucidated. Positive and negative effects of anaerobiosis on environmentally relevant processes and their influence on man and on animals are reviewed. Finally, some examples of the biotechnological application of anaerobic processes are presented.     

The obesity-related pathology and Th17 cells

Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases. We herein outline the developing principles in the control of T cell differentiation and function via their cellular metabolism. Also discussed are recent findings that changes in the intracellular metabolism, including fatty acid metabolism, affect the Th17 cell function in obese individuals. Finally, we will also highlight the unique molecular mechanism involved in the activation of retinoid-related orphan receptor-gamma-t (RORγt) by intracellular metabolism and discuss a new therapeutic approach for treating autoimmune disorders through the inhibition of RORγt.     

Biochemistry of proinflammatory macrophage activation

In the last decade, metabolism has been recognized as a major determinant of immunological processes. During an inflammatory response, macrophages undergo striking changes in their metabolism. This metabolic reprogramming is governed by a complex interplay between metabolic enzymes and metabolites of different pathways and represents the basis for proper macrophage function. It is now evident that these changes go far beyond the well-known Warburg effect and the perturbation of metabolic targets is being investigated as a means to treat infections and auto-immune diseases. In the present review, we will aim to provide an overview of the metabolic responses during proinflammatory macrophage activation and show how these changes modulate the immune response.     

Nucleolar control of p53: a cellular Achilles’ heel and a target for cancer therapy

Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli.     

Mycorrhizas and root architecture

Summary Roots function dually as a support system and as the nutrient uptake organ of plants. Root morphology changes in response to the soil environment to minimize the metabolic cost of maintaining the root system, while maximizing nutrient acquisition. In response to nutrient-limiting conditions, plants may increase root fineness or specific root length (root length per gram root weight), root/shoot ratio, or root hair length and number. Each of these adaptations involves a different metabolic cost to the plant, with root hair formation as the least costly change, buffering against more costly changes in root/shoot ratio. Mycorrhizal symbiosis is another alternative to such changes. Plants with high degrees of dependence on the symbiosis have coarser root systems, less plasticity in root/shoot ratio, and develop fewer root hairs in low-fertility soils. In nutrient-limited soils, plants highly dependent on mycorrhiza reduce metabolic cost by developing an even more coarse or magnolioid root system, which is less able to obtain nutrients and thus creates a greater dependence of the plant on the symbiosis. These subtle changes in root architecture may be induced by mycorrhizal fungi and can be quantified using topological analysis of rooting patterns. The ability of mycorrhizal fungi to elicit change in root architecture appears to be limited to plant species which are highly dependent upon mycorrhizal symbiosis.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.