Journal de la Societe de biologie最新文献

The formation of blood cells and vascular networks occurs simultaneously during development, and both lineages remain in close association in all adult tissues. The functional setting of both systems within the embryo and their renewal during adult life are highly complex processes, and require the involvement of numerous molecular actors, the activities of which are often overlapping. Here, I review the activity of TAL-1, a basic-helix-loop-helix transcription factor, which plays a key role in the formation and functioning of both blood and endothelial systems, with a particular emphasis on recent data that associate TAL-1 with angiogenesis.

Angiogenesis is a basic process during development and in pathology as well. The molecular networks involved in angiogenesis are not totally understood. We have recently developed a new model for tumoral angiogenesis in the chicken embryo, which allows large scale studies. On the other hand we have uncovered a new induction pathway, which involves stress of the endoplasmic reticulum. These investigations open up novel prospects for the future.

The renin-angiotensin system (RAS) is one of the most important systems in physiology and in pathology. The (pro)renin receptor [(P)RR] is a new component of the system that has attracted much attention, being potentially a new therapeutic target, because the binding of renin and of prorenin triggers the activation of the mitogen-activated protein kinase p42/p44 followed by up-regulation of the expression of profibrotic genes. and because prorenin bound to (P)RR becomes catalytically active. The introduction of a renin inhibitor in the treatment of hypertension and of organ damages, together with the discovery of (P)RR, has revived the interest for the RAS and for potential new RAS blockers, in order to optimize RAS blockade in tissues.

Since several decades anti-oxidants have been much studied, and scientists have tried to prove the preventive and curative effects in many chronic diseases. However, it is not uncommon to find highly contradictory clinical results, which may explain that consumers are less enthusiastic for anti-oxidants food supplements. First of all, definitions should be reviewed, such as that of free radicals (FR); all of them are not toxic. Some of them, such as nitric oxide, are necessary for the proper physiological functioning of the body, and eliminating them would be a mistake! However, other reactive oxygen species (ROS), which are not FR, are toxic, such as hydrogen peroxide. We have also redefined the oxidative stress, which it is not only the result of an imbalance between oxidants and anti-oxidants, but also the consequence of imbalance in the cellular redox status. The mechanisms of action, bioavailability, synergy and methods to determine the level of anti-oxidants are very sensitive topics, and it is crucial to study them if we want to obtain reliable clinical studies. Given the failure of clinical studies about anti-oxidant, we try to explain strategies which should be followed. First of all, the nature of the anti-oxidant is important; and an anti-oxidant from a natural origin must be preferred. Then, we proposed that the dose-effect was certainly responsible for the failure of tests. Indeed, doses administered in the studies was either too weak to obtain significant results, or too high, becoming pro-oxidative and eliminating the basal concentration of ROS (physiological role). Involvement of mitochondria and glycation are particularly discussed. Nutrigenomics and nutrigenetics are also discussed, which study the interactions between genetics and nutrition. Genetic polymorphism can explain the variable absorption of micronutrients. This concept leads to a truth believed by all scientists, namely the need to provide the right anti-oxidant, in adequate quantity, at the right place, at the right time and for a particular individual. To increase the anti-oxidant capacity of the body, the exogenous intake of anti-oxidants must be increased or the endogenous synthesis of anti-oxidants (SOD, GPX, GSH) must be stimulated. Targeting mitochondria and increasing their overall anti-oxidant defence system will be a challenge. Increasing the bioavailability of anti-oxidants and studying their passage through the blood-brain barrier must be also taken in consideration.

There is considerable evidence that the human brain maintains the ability to reorganize itself throughout life, an ability known as neuroplasticity. Initially demonstrated in physiological situations, neuroplasticity includes, and relies on, a number of adaptive mechanisms that include not only phenotypic modifications of neurons or synaptic reorganisation but also major modifications of brain circuitry after insults. Recently, the presence of neurogenic zones in the adult brain has unveiled a new aspect of brain plasticity that, together with emerging stem cell therapy, opens the possibility to take advantage of these natural reminders of the developmental period to repair lesioned tissues, a concept known as "therapeutic plasticity".

Rgulations on seeds and varieties established 80 years ago proved to be to be efficient for European agriculture. Genetic progress for many traits, such as yield resistance to pests and diseases, have been observed for all cultivated crops. Plant variety protection by the UPOV (Union Internationale pour la Protetion Végétable) sytem came into being with the adoption of the International Convention for the Protection of New Varieties of Plants by a diplomatic conference in Paris on December 2, 1961. At this point the rights of plant breeders were recognized on an international basis. The UPOV Convention provides a sui generis form of intellectual property protection which has been specifically adapted for the process of plant breeding and has been developed with the aim of encouraging breeders to develop new varieties of plants. In contrast, the European GM regulation is very difficult to apply, very expensive and limits the development of biotechnology in Europe, as well for research as for development.

The endothelium, lining the inner side of all vessel types, is constituted of a monolayer of endothelial cells with cobblestone morphology. Endothelial cell-cell contacts contain numerous transmembrane adhesive proteins that are either clustered in junctional structures or located along the intercellular cleft. These proteins promote cell-cell adhesion and control vascular permeability to fluids and molecules, as well as transmigration of various types of leukocytes. In addition, recent findings showed that constituents of the junctions might be part of the vascular invasion machinery by activating cell protrusions. Such activities may thus be considered as markers of pathological angiogenesis or targets of antiangiogenic therapy.

The surgeon must know the importance of angiogenesis in wound healing. He must also use anti-angiogenics to change the clinical situations and make curative a potentially ineffective surgery. However, these strategies require daily biological indicators able to quantify the tissue activity, that we do not possess yet, nor have we any indicator to predict tumour sensitivity to anti-angiogenics.

In contrast to monoaminergic (MA-ergic) neurons possessing the whole set of the enzymes for MA synthesis from the precursor amino-acid, some, mostly peptidergic, neurons co-express only one of the enzymes of monoamine synthesis. They are widely distributed in the brain, being particularly numerous in ontogenesis and, in adulthood, under certain physiological conditions. Most monoenzymatic neurons possess one of the enzymes for dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). TH and AADC are enzymatically active in a substantial number of monoenzymatic neurons, where they are capable of converting L-tyrosine to L-3,4-dihydroxy-phenylalanine (L-DOPA) and L-DOPA to dopamine (DA) (or 5-hydroxy-tryptophan, 5-HTP to serotonin), respectively. According to our data L-DOPA synthesized in monoenzymatic TH-neurons is released and taken up by monoenzymatic AADC-neurons for DA synthesis. Moreover, L-DOPA captured by dopaminergic neurons and serotoninergic neurons serves to stimulate dopamine synthesis in the former and to start DA synthesis in the latter. Cooperative synthesis of MAs is considered as a compensatory reaction under a failure of MA-ergic neurons, e.g. in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease, which are developed primarily because of degeneration of DA-ergic neurons of the tuberoinfundibular system and the nigrostriatal system, respectively. Noteworthy, the neurotoxin-induced increase of prolactin secretion returns with time to a normal level due to the stimulation of DA synthesis by the tuberoinfundibular most probably monoenzymatic neurons. The same compensatory mechanism is supposed to be used under the failure of the nigrostriatal DA-ergic system that is manifested by an increased number of monoenzymatic neurons in the striatum of animals with neurotoxin-induced parkinsonism and in humans with Parkinson's disease. Expression of the enzymes of MA synthesis in non-monoaminergic neurons is controlled by intercellular signals such as classical neurotransmitters (catecholamines), etc. Thus, a substantial number of brain neurons express partly the monoaminergic phenotype, namely individual complementary enzymes of MA synthesis, serving to produce MAs in cooperation, which is considered as a compensatory reaction under the failure of MA-ergic neurons.

The vertebrate neuron axon has long been considered as devoid of the protein synthesis machinery. During the early nineties however, the cytochemical visualization of identified mRNAs within certain rodent neuron axons challenged this dogma of cellular neurobiology. The aim of this paper is to illustrate, taking mainly the mouse olfactory system as an example, conceptual and methodological approaches developed in particular in my group, that aim at identifying the function of these axonal mRNAs.