Comptes rendus des seances de la Societe de biologie et de ses filiales最新文献

Matrix metalloproteinases (MMPs) and growth factors such as hepatocyte growth factor (HGF) are implicated in tumoral progression of several digestive cancers. The rat DHD/K12 colonic cancer cell line is very invasive in vivo. We showed by RT-PCR and western immunoblotting the presence of HGF receptor, c-Met, in DHD/K12 cells. Then, we detected by zymography and western blots the secretion of MMP-2 and MMP-9 in the conditioned medium of these cells. After 24 or 48 h of culture in medium supplemented with HGF, transforming growth factor-alpha (TGF-alpha) or sodium butyrate, MMP production by DHD/K12 cells was stimulated by HGF and TGF-alpha and inhibited by sodium butyrate. Knowing the capacity of MMPs to degrade the extracellular matrix and thus to favour tumoral invasion, results suggest that HGF is implicated in the aggressive behaviour of DHD/K12 cells since it increased MMPs secretion by these cells.

This review focuses on the mechanism(s) of action of neurotoxins acting on the inactivation of voltage-gated Na channels. Na channels are transmembrane proteins which are fundamental for cellular communication. These proteins form pores in the plasma membrane allowing passive ionic movements to occur. Their opening and closing are controlled by gating systems which depend on both membrane potential and time. Na channels have three functional properties, mainly studied using electrophysiological and biochemical techniques, to ensure their role in the generation and propagation of action potentials: 1) a highly selectivity for Na ions, 2) a rapid opening ("activation"), responsible for the depolarizing phase of the action potential, and 3) a late closing ("inactivation") involved in the repolarizing phase of the action potential. As an essential protein for membrane excitability, the Na channel is the specific target of a number of vegetal and animal toxins which, by binding to the channel, alter its activity by affecting one or more of its properties. At least six toxin receptor sites have been identified on the neuronal Na channel on the basis of binding studies. However, only toxins interacting with four of these sites (sites 2, 3, 5 et 6) produce alterations of channel inactivation. The maximal percentage of Na channels modified by the binding of neurotoxins to sites 2 (batrachotoxin and some alkaloids), 3 (alpha-scorpion and sea anemone toxins), 5 (brevetoxins and ciguatoxins) et 6 (delta-conotoxins) is different according to the site considered. However, in all cases, these channels do not inactivate. Moreover, Na channels modified by toxins which bind to sites 2, 5 and 6 activate at membrane potentials more negative than do unmodified channels. The physiological consequences of Na channel modifications, induced by the binding of neurotoxins to sites 2, 3, 5 and 6, are (i) an inhibition of cellular excitability due to an important membrane depolarization (site 2), (ii) a decrease of cellular excitability due to an important increase in the action potential duration (site 3) and (iii) an increase in cellular excitability which results in spontaneous and repetitive firing of action potentials (sites 5 and 6). The biochemical and electrophysiological studies performed with these toxins, as well as the determination of their molecular structure, have given basic information on the function and structure of the Na channel protein. Therefore, various models representing the different states of Na channels have been proposed to account for the neurotoxin-induced modifications of Na inactivation. Moreover, the localization of receptor binding sites 2, 3, 5 et 6 for these toxins on the neuronal Na channel has been deduced and the molecular identification of the recognition site(s) for some of them has been established on the alpha sub-unit forming the Na channel protein.

Neuropeptides play a crucial role in cell communication as neurotransmitters, neuromodulators or neurohormones, and are involved in a number of biological activities including neuroendocrine regulations, control of neurovegetative functions, trophic effects and modulation of the immune response. The number of neuropeptides that have been fully characterized so far is rather limited, as compared to the number of precursor proteins that are actually expressed in nerve cells. Owing to the development of powerful analytical and structural identification methods, and the rapid advance in molecular biology techniques, a number of novel neuropeptides have been characterized during the last decade, in both vertebrates and invertebrates. The aim of the present review is to provide a comprehensive coverage of the different approaches which are currently used to identify novel neuropeptides.

About 30% of infertilities are from male origin. They appear in some cases de novo and considered idiopathic. The aim of our work is to evaluate, in these cases, the Y chromosome long arm microdeletion prevalence within the AZF a, b and c regions by molecular biology technics. Were excluded from our study, azoo-oligospermia from hereditary, endocrine, obstructive origins or with a constitutional cytogenetic abnormality. 48 infertile men with a spermogram-proven azoo-oligospermia were studied. Among them, 30 were idiopathics, 8 out of them exhibited a genital infection past history or biological abnormalities suggesting partial obtruction of the genito-urinary tractus. 8 cases of varicocela and 10 of cryptorchidia were also studied. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the 3 Y chromosome AZF zones. PCR products were then analysed on agarose gels. Considering the difficulty to affirm the absence of a signal in molecular biology, each suspicion of deletion was checked by multiplex PCR complication with the SRY marker. 5 Y chromosome long arm microdeletions were diagnosed among our 48 patients. All of them included the AZFc zone and the intragenic DAZ gene markers. Moreover a larger Y chromosome deletion encompassing the 3 AZF zones was diagnosed, and confirmed by the cytogenetic analysis. All the Y chromosome microdeletions were observed in the 22 truly idiopathic azoo/oligospermia, corresponding to a proportion of 22.7% which falls to 10.4% considering the whole population of 48 studied people (closer to the published data). The relatively high proportion of microdeletions found in our series, underlines the need of a strict patient selection to avoid unnecessary search for long arm Y chromosome microdeletions.

Calcium channel blockers are also termed calcium antagonists or calcium entry blockers. The use of calcium antagonists for the management of hypertension is well established. Their control of vascular tone is related to their interaction with the alpha 1 subunit of L-type calcium channels. This interaction is not simple since prolonged depolarisation promotes the inactivated state of the channels resulting in a change of affinity which is different for various molecules so far considered. The isoforms of alpha 1 subunits and the duration of the stimulus required to activate heart or vessels are important parameters to be considered with the nature of the molecule. Those parameters influence the vascular selectivity which is quantified as the ratio of the concentrations required to reduce by 50% the contraction of heart and of vessels. This selectivity is an important component in the therapeutic action. Another component of this action is the prevention of structural changes noted in heart and arteries. As well as lowering blood pressure, calcium channel blockers have also been found to exert blood pressure independent effects. For instance, they reduce cardiac and vascular hypertrophy and avoid renal damage. In the stroke-prone rat, such protective effects are accompanied by reduction of the salt-dependent overexpression of the gene of endothelin-1 and of fetal genes associated with cardiac hypertrophy. This paper summarizes available information about those components and discuss their significance.

Annexins are a family of proteins present within the tissues of all multicellular organisms, mammalian erythrocytes excepted. The property shared by all annexins is the calcium and membrane binding. Annexins are constituted of two domains. The N-terminal domain gives the molecule its specificity and the C-terminal domain, highly conserved, containing 4 repetitions of 70 amino-acids, gives the common properties. Although numerous important works were performed, the exact function of annexins is not unraveled. They participate to many cellular processes as for instance exocytosis, endocytosis or phagosome maturation. Many hypotheses, supported by experimental results, have been proposed. In this review, we propose a summary of the principal characteristics of annexins and we discuss the main hypotheses proposed for their functions.

Psychoactive drugs are used almost universally for the pleasure and benefits which they can provide, but they also cause sufficient harm that most societies have adopted policies to control and limit the amount of use. Science is increasingly called upon to provide a rational basis for these policies. However, the biological sciences and modern sociology have fundamentally different approaches to such issues, the former being based on the concept that there is an external reality which can be discovered only by objective means, the latter holding that social problems are defined strictly subjectively and can not be separated from the values and ideologies of the researchers. Since social policy affects all members of a society, and must reflect all of their attitudes, values and traditions, science can contribute only facts and probabilities, but society as a whole must assign the values and make the required choices.

It is well known that Helicobacter pylori can cause gastritis, gastroduodenal ulcers and malignant diseases. The infiltration of polymorphonuclear leukocytes is recognized in the lesions of these diseases, and the infiltration disappears by antibiotic therapy. However, it is not yet clarified how Helicobacter pylori induces the formation of lesions including leukocyte infiltration. Recently, we have confirmed that several kinds of cytokines are expressed in the gastric biopsy specimens of gastroduodenal diseases. Especially, it is conjectured that chemokines such as interleukin-8 (IL-8) which are expressed in the specimens, induce leukocyte infiltration, gastric mucosal inflammation and gastroduodenal ulcers. It is possible that Helicobacter pylori CagA gene is closely related with IL-8 expression because this cytokine is more strongly expressed in the specimens from the patients infected with CagA-positive Helicobacter than those with CagA-negative one.

Among the opioid receptors family, the cloning of the mu, kappa and delta receptors was followed by that of another member, named ORL1 (Opiate Receptor Like 1). In spite of obvious homologies with the mu, kappa and delta receptors, ORL1 does not display a relevant affinity for the endogenous ligands of these former receptors (beta endorphin, enkephalins, dynorphin A...). This observation has prompted to search for an endogenous ligand of ORL1. A heptadecapeptide which fulfils this function, with a nanomolar affinity, has been found. It was named either nociceptin or orphanin FQ. It demonstrates, according either to the dose or to the route of administration, hyperalgesic, allodynic, antiopioidergic or even analgesic effects. It displays also many behavioural effects, modifying especially locomotion, exploratory behaviour, motivation, anxiety, memory, food intake. Nociceptin results from the cleavage of a large precursor protein, prepronociceptin (PPNOC). In this latter, nociceptin is flanked on its C-terminal region by another peptide which may be regarded either as a heptadecapeptide (NocII), or a bidecapeptide (NocIII) according to the inclusion or not of a fragment constituted by 3 arginine residues. Investigating the functions modulated by NocII, we observed that it stimulates locomotor activity of mice and shortens the forepaws licking latency in the hot plate test (55 degrees C); these effects are not shared by NocIII. The simultaneous administration of NocII and nociceptin resulted in animals put on the hot plate to the appearance of their respective effects, not modified by the presence of the other. A 41 amino acid peptide flanks nociceptin on its N-terminal region in PPNOC. It may be cleaved to generate a heptadecapeptide, named nocistatin on account of its antagonist effect on the hyperalgesia/allodynia induced by nociceptin. Thus, the discovery of ORL1 has led to that of nociceptin, that of its precursor PPNOC, and thereby to that of NocII/NocIII and nocistatin. The functions modulated by these peptides are being investigated whereas their receptors are yet unknown. These multiple targets allow to expect new strategies to modulate their functions.