Ceramide: physiological and pathophysiological aspects

Ceramide generated in the cell membrane has been shown to be central for the induction of apoptosis by death receptors and many stress stimuli such as gamma-irradiation, UV-light or infection with pathogens. Ceramide reorganizes cell membranes and forms large ceramide-enriched membrane domains that serve the spatial and temporal organization of the cellular signalosome upon activation. Thus, ceramide-enriched membrane domains mediate clustering of CD95 and DR5 to facilitate apoptosis, and they are also critically involved in apoptosis after irradiation, UV-light and infection with Pseudomonas aeruginosa. Since ceramide-enriched membrane domains amplify signals, their function is not restricted to the induction of apoptosis and it was shown that ceramide-enriched membrane domains are also involved in internalization of pathogens and the control of cytokine release from infected epithelial cells. Recent studies support the notion that changes of the ceramide metabolism are also critically involved in human diseases, for instance neurological disorders, cancer, infectious diseases and Wilson's disease.     

Erythrocyte deformability: physiological aspects

Analysis of published and author's data on the physiological role of deformability of erythrocytes, general mechanisms of modifications and disturbances, assessment methods, and the role of this blood feature for assessing the body status. This parameter is one of the most labile features of blood that shows highly sensitive reaction to practically any changes in metabolic process in erythrocytes and in a whole body. Degradation of deformability of erythrocytes under various types of oxygen deficit deteriorates functioning of the system of oxygen transportation at various levels: heart, vascular flow, oxygen-transporting blood function. Under hypoxia the parameters of oxygen-transporting blood function, of peroxide oxidation of lipids and of the antioxidation system correlate well with degradation of deformability of erythrocytes. Therefore, this parameter can be used an integrated criterion of disturbances in oxygen supply, and of prooxidation-antioxidation body status. Deformability of erythrocytes is a factor generating adequate the oxygen supply to tissue, and its degradation aggravates substitution of the oxidase pattern of oxygen utilization with the oxygenase pattern. This parameter is extremely important for the body functional status.     

Neurosteroids: behavioral aspects and physiological implications]

The term "neurosteroids" applies to those steroids that are both formed in the nervous system from sterol precursors, and accumulate in the nervous system, at least in part, independently of peripheral steroidogenic glands secretion. Neurosteroids that are active on the central nervous system include, mainly, pregnenolone (PREG), dehydroepiandrosterone (DHEA) and their sulfate esters (PREG-S and DHEA-S), as well as the reduced metabolite of progesterone, 3 alpha,5 alpha-TH PROG also called allopregnanolone. These neuroactive neurosteroids alter neuronal excitability by modulating the activity of several neurotransmitter receptors and thus can influence behavior. PREG-S decreases the sleeping time in rats anesthetized with a barbiturate, which is consistent with its antagonist action on the GABAA receptor (GABAA-R). Allopregnanolone is anxiolytic in rats tested in a conflict paradigm, through an interaction at a site specific for the benzodiazepine (BZ) receptor inverse agonist RO15-4513 and/or at the picrotoxinin site on GABAA-R. The contribution of the amygdala, a key region involved in the control of anxiety, is also demonstrated for the anxiolytic action of allopregnanolone. An anti-agressive effect of DHEA can be observed in castrated male mice who become agressive in the presence of lactating females. This inhibition of agressiveness by DHEA is associated to a selective decrease in the brain of PREG-S, which may, in turn, trigger an increase of endogenous GABAergic tone. Finally, cognitive performances of aged rats tested in the Morris water maze and the Y-maze can be correlated with individual concentrations of PREG-S in the hippocampus, i.e. poor performance in both tasks with low levels of PREG-S. Remarkably, the memory deficits are significantly improved, albeit transiently, by an intra-hippocampal injection of PREG-S in impaired aged rats. Promnesiant PREG-S may then reinforce some neurotransmitter systems that can decline with age. This brief review provides evidence of the pharmacology and physiological correlates of neurosteroids involved in behavioral phenomena. However, neurobiological mechanisms of behavioral effects of neurosteroids await further investigation.     

Analysis of PCB-degrading bacteria : physiological aspects

Several aerobic co-cultures capable of co-metabolizing polychlorinated biphenyls (PCBs) were acquired by cultivation on biphenyls (BP). The source of micro-organisms was PCB-contaminated soil taken from various sites in the Czech Republic. Several bacterial strains (Gram-negative rods) were isolated, and their capacity to degrade Delor 103 (a PCB mixture containing di- to hexachlorobiphenyls) was analysed. This study was focused on co-culture 319 and isolate 2. The growth parameters of both those cultures were studied on BP ; for isolate number 2 the specific growth rate μ = 0·122 (h⁻¹) was calculated. The degradation of the individual congeners was estimated and resulted in more than 50% of the degradation of nearly all congeners during a 2-week experiment. Toxicity of Delor 103 on the vitality of the cells was followed by using viable plate count. The viability of the tested strain was preserved in the 100 times higher Delor 103 concentration compared with conditions in degradation experiments.     

GABA-benzodiazepine interactions: physiological, pharmacological and developmental aspects

Many of the pharmacological actions of the benzodiazepines can be attributed to their actions on gamma-aminobutyric acid (GABA) systms in the brain. Electrophysiological studies on dorsal raphe neurons indicate that the benzodiazepines act postsynaptically to potentiate GABAergic inhibition in this midbrain nucleus. Direct binding studies have shown that both in vitro and in vivo binding of [3H]diazepam to a specific high affinity benzodiazepine binding site in cerebral cortical tissue are enhanced by the direct in vitro addition of GABA and GABA agonists or by pretreatment of animals with GABA analogs and agents that elevate GABA levels in brain. Ontogenic development of [3H]diazepam binding in brain parallels the development of the sodium-independent [3H]GABA binding. The ability of GABA to enhance benzodiazepine binding is present throughout development and inversely related to age. These data suggest that there is a functionally significant interaction between the benzodiazepines and GABA throughout development and at maturity. A model is proposed to relate these interactions to conformational changes in a benzodiazepine/GABA/Cl- ionophore complex.     

Biochemical and physiological aspects of anhydrobiosis

• 1.1. The biochemical and physiological mechanisms which are involved in anhydrobiotic survival have been reviewed.
• 2.2. The physical state of water within hydrated and dehydrated organisms is discussed in relation to the concepts of “free” and “bound” water and to the “vicinal water network model” of Clegg (1979) Cell Associated Water. Academic Press, New York.
• 3.3. Evidence is presented for the replacement of “bound” water by glycerol in dried embryos of Artemia salina, but the role of high glycerol content in the free-living nematode Aphelenchus avenae has yet to be evaluated.
• 4.4. The adaptive significance of trehalose is shown to lie in the fact that because it is a non-reducing sugar, it will not participate in a “browing” reaction between reduced groups of sugars and free amino groups of dry proteins. Trehalose also inhibits “browning” reactions between reducing sugars and dry proteins.
• 5.5. The effect of dehydration on membrane permeability suggests that dried organisms suffer mostly if placed directly into a revival medium due to leakage through structurally deformed membrane systems.
• 6.6. Glycerol and trehalose may interact with lipid membranes and reduce the amount of leakage.
• 7.7. Damage to membranes caused by lipid peroxidation is discussed.
• 8.8. Results suggest that the role of high lipid contents in nematode anhydrobiotes is essentially that of a food reserve, although the morphological distribution of such lipid may be important in maintaining the spatial distribution of body tissues in the absence of bulk water.

     

Antizyme inhibitor 2: molecular, cellular and physiological aspects

Polyamines are small organic polycations essential for cell proliferation and survival. Antizymes (AZs) are small proteins regulated by polyamines that inhibit polyamine biosynthesis and uptake in mammalian cells. In addition, antizyme functions are also regulated by antizyme inhibitors, homologue proteins of ornithine decarboxylase lacking enzymatic activity. There are two antizyme inhibitors (AZIN), known as AZIN1 and AZIN2, that bind to AZs and negate their effects on polyamine metabolism. Here, we review different molecular and cellular properties of the novel AZIN2 with particular emphasis on the role that this protein may have in brain and testis physiology. Whereas AZIN1 is ubiquitously found in mammalian tissues, AZIN2 expression appears to be restricted to brain and testis. In transfected cells, AZIN2 is mainly located in the endoplasmic reticulum–Golgi intermediate compartment and in the cis-Golgi network. AZIN2 is a labile protein that is degraded by the proteasome by a ubiquitin-dependent mechanism. Regarding its physiological role, spatial and temporal analyses of AZIN2 expression in the mouse testis suggest that this protein may have a role in spermiogenesis.     

The avian oesophageal motor function and its nervous control: some physiological, pharmacological and comparative aspects.

1. This paper deals with the avian oesophageal motor function and it attempts to draw some comparative aspects between neural regulation of the avian and mammalian oesophagus. 2. Different from the mammalian oesophagus, the avian oesophagus, presents at rest electrical activity associated to spontaneous contractions. 3. Swallowing elicits peristaltic contraction, characterized by an inhibitory and an excitatory component. 4. Non-adrenergic, non-cholinergic neurons are responsible for the inhibitory component. 5. Contrarily to what observed in mammals, where the peripheral mechanism are important for the peristaltic sequence, the primary peristaltism of birds seems to be entirely mediated by extrinsic nervous system.     

Biochemical and physiological aspects of ubiquinone function

The brief review presents evidence that, in addition to the well-known functions of ubiquinone (coenzyme Q) as a component of the mitochondrial respiratory chain, this compound in the reduced form (ubiquinol) functions as an antioxidant. Ubiquinone in a partially reduced form is found in all cell membranes. It protects efficiently not only membrane phospholipids from peroxidation but also mitochondrial DNA and membrane proteins from free-radical-induced oxidative damage. This protective role of ubiquinol is independent of the effect of exogenous antioxidants, such as vitamin E, and it can both prevent the formation of free lipid radicals and eliminate them either directly or by regenerating vitamin E.     

Comparative effects of four herbicides on physiological aspects in Triticum sativum L.

Four herbicide (topik, puma super, granstar and derby) treatments at the recommended field dose (RFD) were applied for 5 weeks on wheat (Triticum sativum L. cv. Giza 168) crop. These selected herbicides are recommended to control two types (narrow and broad) of weeds in this crop. The growth parameter, oxidative stress defence system, nitrate reduction, proline level and protein contents were used to evaluate the toxic effect of these herbicides on wheat crop. The toxicity of herbicides used on this crop was as follows: puma super > topik > derby > granstar. The correlation between the herbicide concentrations and the activities of the antioxidant enzymes was monitored.