Different molecular mechanisms for cAMP regulation of gene expression during Dictyostelium development

Alterations in cAMP concentrations have been implicated in developmentally regulated gene expression in Dictyostelium. Using a variety of culture conditions to control the metabolism of cAMP during cytodifferentiation, I have examined the role of the cyclic nucleotide in development. Conditions which allow intracellular synthesis of cAMP promote the normal developmental repression of gene M4-1 by a mechanism which is completely independent of the formation of multicellular aggregates. If, however, cells are inhibited in their ability to activate adenylate cyclase and, thus, intracellular cAMP signaling, they prove unable to repress M4-1, even in the presence of exogenous cAMP. In contrast, expression of genes which exhibit maximal activity after aggregate formation depends upon accumulation of extracellular cAMP. Inhibition of intracellular cAMP signaling does not prevent the expression of these genes if cultures are simultaneously exposed to high levels of exogenously added extracellular cAMP. These results indicate that there are at least two independent mechanisms involved in the developmental regulation of gene expression by cAMP in Dictyostelium. I discuss plausible molecular mechanisms through which cAMP might alter gene expression.     

Acid-base regulation in fishes: cellular and molecular mechanisms

The mechanisms underlying acid-base transfers across the branchial epithelium of fishes have been studied for more than 70 years. These animals are able to compensate for changes to internal pH following a wide range of acid-base challenges, and the gill epithelium is the primary site of acid-base transfers to the water. This paper reviews recent molecular, immunohistochemical, and functional studies that have begun to define the protein transporters involved in the acid-base relevant ion transfers. Both Na(+)/H(+) exchange (NHE) and vacuolar-type H(+)-ATPase transport H(+) from the fish to the environment. While NHEs have been thought to carry out this function mainly in seawater-adapted animals, these proteins have now been localized to mitochondrial-rich cells in the gill epithelium of both fresh and saltwater-adapted fishes. NHEs have been found in the gill epithelium of elasmobranchs, teleosts, and an agnathan. In several species, apical isoforms (NHE2 and NHE3) appear to be up-regulated following acidosis. In freshwater teleosts, H(+)-ATPase drives H(+) excretion and is indirectly coupled to Na(+) uptake (via Na(+) channels). It has been localized to respiratory pavement cells and chloride cells of the gill epithelium. In the marine elasmobranch, both branchial NHE and H(+)-ATPase have been identified, suggesting that a combination of these mechanisms may be utilized by marine elasmobranchs for acid-base regulation. An apically located Cl(-)/HCO(3)(-) anion exchanger in chloride cells may be responsible for base excretion in fresh and seawater-adapted fishes. While only a few species have been examined to date, new molecular approaches applied to a wider range of fishes will continue to improve our understanding of the roles of the various gill membrane transport processes in acid-base balance.     

Immune regulation by helminth parasites: cellular and molecular mechanisms

Immunology was founded by studying the body's response to infectious microorganisms, and yet microbial prokaryotes only tell half the story of the immune system. Eukaryotic pathogens--protozoa, helminths, fungi and ectoparasites--have all been powerful selective forces for immune evolution. Often, as with lethal protozoal parasites, the focus has been on acute infections and the inflammatory responses they evoke. Long-lived parasites such as the helminths, however, are more remarkable for their ability to downregulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.     

Possible mechanisms of information interactions in molecular physico-biological systems]

Cooperative mechanisms of information transfer in molecular physico-biological systems are suggested. Expressions for probability of cooperative emission from interacting molecules having quite definite information about the character of distribution of molecules inside the system are derived. The suggested mechanisms of information transfer on the atomic-molecular level will possibly allow to understand better and to describe adequately many interesting phenomena considered by molecular biology and molecular psychobiology in particular. Appendix: Throbbing in cooperative luminescence for triads of molecules combined with each other by weak interaction.     

基因表达调控多面手——microRNA和siRNA的作用机制

miRNA(microRNA)是一类广泛存在于高等真核细胞中的长度约为21个碱基的小分子非编码RNA,参与调控三分之一以上基因的表达,并与多种人类疾病存在重要关联。而siRNA(small interfering RNA)是RNA干扰(RNA interference,RNAi)中的效应分子,其结构和作用机制与miRNA存在许多类似之处。由于miRNA和siRNA具有重要的生物学功能。因此,对它们作用机制的理解具有非常重要的理论意义和应用指导价值。该综述将对它们作用机制的研究进展做一总结和回顾。     

Ion regulation in fish gills: recent progress in the cellular and molecular mechanisms

Fish encounter harsh ionic/osmotic gradients on their aquatic environments, and the mechanisms through which they maintain internal homeostasis are more challenging compared with those of terrestrial vertebrates. Gills are one of the major organs conducting the internal ionic and acid-base regulation, with specialized ionocytes as the major cells carrying out active transport of ions. Exploring the iono/osmoregulatory mechanisms in fish gills, extensive literature proposed several models, with many conflicting or unsolved issues. Recent studies emerged, shedding light on these issues with new opened windows on other aspects, on account of available advanced molecular/cellular physiological approaches and animal models. Respective types of ionocytes and ion transporters, and the relevant regulators for the mechanisms of NaCl secretion, Na(+) uptake/acid secretion/NH(4)(+) excretion, Ca(2+) uptake, and Cl(-) uptake/base secretion, were identified and functionally characterized. These new ideas broadened our understanding of the molecular/cellular mechanisms behind the functional modification/regulation of fish gill ion transport during acute and long-term acclimation to environmental challenges. Moreover, a model for the systematic and local carbohydrate energy supply to gill ionocytes during these acclimation processes was also proposed. These provide powerful platforms to precisely study transport pathways and functional regulation of specific ions, transporters, and ionocytes; however, very few model species were established so far, whereas more efforts are needed in other species.     

The cellular mechanisms and regulation of metastasis formation

Data accumulating in biochemistry, molecular and cell biology, and experimental oncology indicate that metastasis, which is the formation of secondary tumor growth foci during cancer progression, is a highly determinate and regulated process. The process includes the emergence of a metastatic cell population possessing special properties to allow cell dissemination and seeding in distant organs and the formation of a specific microenvironment in target organs. Among other changes, metastatic cells display plasticity, being capable of switching their motility to the most efficient mode depending on the properties of surrounding tissues; start expressing specific surface receptors to ensure their migration to target organs; and acquire certain features of stem cells, being capable of surviving and reproducing in an alien microenvironment. A specific niche, known as the premetastatic niche, develops in the target organ in a strong coordination with the above changes to stimulate the initiation and growth of a prospective metastasis. The review considers the recent findings related to the mechanisms that regulate the emergence of the metastatic cell population, the formation of premetastatic niches, and the coordination of the two processes.     

Amino acids as regulators of gene expression: molecular mechanisms

Regulation of gene expression by nutrients in mammals is an important mechanism allowing them to adapt their physiological functions according to the supply of nutrient in the diet. It has been shown recently that amino acids are able to regulate by themselves the expression of numerous genes. CHOP, asparagine synthetase, and IGFBP-1 regulation following AA starvation will be described in this review with special interest in the molecular mechanisms involved.