Low-Dose Curcumin Stimulates Proliferation,Migration and Phagocytic Activity of Olfactory Ensheathing Cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies.     

Aspergillus penicillioides—a true halophile existing in hypersaline and polyhaline econiches

Aspergillus penicillioides is a true halophile, present in diverse econiches from the hypersaline athalassohaline Dead Sea and the thalassohaline solar salterns, to the polyhaline estuaries and mangroves of Goa-India. Thirty-nine isolates from these environments were seen to be moderate halophiles, stenohaline or euryhaline in nature, with comparable salt tolerance indices. They had an obligate need for a low water activity and were unable to grow on a regular defined medium such as Czapek Dox Agar, or on various nutrient rich agar media such as Malt Extract, Potato Dextrose and Sabouraud Agar; however, growth was obtained on all these media when amended with 10 % solar salt. In the absence of added salt, the conidia either did not germinate, or when germinated, distortions and lysis were seen in the short mycelial forms; on media with salt, the mycelia and vesicles appeared normal.     

A role for CCAAT/enhancer-binding protein in hepatic expression of thrombin-activable fibrinolysis inhibitor

Thrombin-activable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase B-like zymogen that upon activation by thrombin, thrombin-thrombomodulin, or plasmin attenuates fibrin clot lysis by inhibiting positive feedback in the fibrinolytic cascade. The concentration of TAFI in plasma varies in the human population and thus may constitute a risk factor for thrombotic disorders. In addition, TAFI has been reported to be a positive acute phase reactant in mice. We have initiated molecular analysis of the human TAFI promoter to understand the mechanisms underlying regulation of TAFI gene expression. We identified a putative C/EBP-binding site between -53 and -40 of the promoter. Mutations in this site that abolish C/EBP binding decrease TAFI promoter activity in human hepatoma (HepG2) cells by approximately 80%. Gel mobility shift analyses indicated that C/EBP-beta present in HepG2 nuclear extracts and C/EBP-alpha and -beta present in adult rat liver nuclear extracts bind to the C/EBP site. C/EBP-alpha, -beta, and -delta isoforms are all capable of binding to the C/EBP site and activating the TAFI promoter. The identification of a functional C/EBP-binding site in the human TAFI promoter may have important implications for the regulation of expression of this gene during development and in response to inflammatory stimuli.     

The involvement of cyclosporin A binding proteins in regulating and uncoupling mitochondrial energy transduction.

The uncoupling of mitochondrial energy transduction by excess Ca2+ may be a factor in the pathogenesis of tissue injury brought about by energy deprivation, for example, in ischaemia. In isolated mitochondria the lesion appears as a large, 20 A, pore in the inner membrane. The pore is blocked potently by the immunosuppressant cyclosporin A. Cyclosporin A also markedly retards collapse of the mitochondrial inner membrane potential in energy-deprived (respiration-inhibited) cardiomyocytes as judged by changes in rhodamine 123 fluorescence, and prolongs cell viability. A potential mitochondrial target for cyclosporin A is the matrix protein cyclophilin. Purified cyclophilin activates the respiratory chain of submitochondrial particles. This might reflect not only a physiological function of this protein, but also a component involved in the generation of the 20 A pore under pathological conditions.     

Reproductive behaviour and vibratory communication of the neotropical predatory stink bug Podisus nigrispinus

Vibratory communication during reproductive behaviour is less well described in predatory (Asopinae) than in phytophagous (Pentatominae) stink bugs. Different steps in the mating behaviour of the predatory stink bug Podisus nigrispinus (Dallas) (Hemiptera: Pentatomidae; Asopinae) are described in the present study, together with vibratory signals emitted on artificial and natural substrate during courtship and copulation. Vibratory signals in Podisus nigrispinus have a decisive role in copulation success and are produced in both sexes by abdominal vibration and tremulation. In P. nigrispinus, one species‐specific female and two male songs, which do not show the calling function typically found in phytophagous stink bugs, are produced by abdominal vibration and are emitted during reproductive behaviour. Additionally, P. nigrispinus produces tremulatory signals that have no species or sex specificity. Tremulatory signals emitted spontaneously on a plant as a sequence of readily repeated pulses are similar to the calling songs of the Pentatominae stink bug. These signals may carry information on the presence of a mate; however, in other behavioural contexts, they may have a different function, such as advertisement or even alarm signals. Plants transmit vibratory signals produced by both mechanisms as a low‐pass filter, increasing the amount of low‐frequency components. The results of the present study raise important questions about the interaction between chemical and vibratory signals in the mating behaviour of predatory stink bugs.     

Characterization and localization of an ATP diphosphohydrolase activity (EC 3.6.1.5) in sarcolemmal membrane from rat heart

In the present report we describe an ATP diphosphohydrolase (apyrase EC 3.6.1.5) in rat cardiac sarcolemma. It is Ca2+ dependent and is insensitive to ouabain, orthovanadate, N-ethylmaleimide (NEM), lanthanum, and oligomycin that are classical ATPase inhibitors. Sodium azide that is a mitochondrial inhibitor at low concentrations, did not affect the enzyme activity at 5.0 mM or below. In contrast, at high concentrations (> 10 mM) sodium azide inhibited the enzyme. Levamisole, a specific inhibitor of alkaline phosphatase and P1, P5-di(adenosine 5-)pentaphosphate (Ap5A), a specific inhibitor of adenylate kinase did not inhibit the enzyme. Mercury chloride showed a parallel inhibition of the hydrolysis of both substrates of apyrase. Similar inhibition profiles are powerful evidence for a common catalytic site for the hydrolysis of both substrates. The enzyme has an optimum pH range of 7.5–8.0 and catalyzes the hydrolysis of triphospho- and diphosphonucleosides other than ATP or ADP. The apparent Km (Michaelis constant) and Vmax (maximal velocity) are 62.1 ± 5.2 M and 1255.7 ± 178 mol inorganic phosphate liberated/min/mg with ATP and 59.4 ± 4.3 M and 269.2 ± 39 mol inorganic phosphate liberated/min/mg with ADP. Enzyme markers indicated that this apyrase is associated with the plasma membrane. A deposition of lead phosphate granules on the outer surface of the sarcolemmal vesicles was observed by electron microscopy in the presence of either ATP or ADP as substrate. It is suggested that the ATP diphosphohydrolase could regulate the concentration of extracellular adenosine, and thus is important in the control of vascular tone and coronary flow.