Modulatory effect of copper on nonenzymatic antioxidants in freshwater fish Channa punctatus (Bloch.)

Effect of the low level of copper exposure on nonenzymatic antioxidants was studied in a freshwater fish Channa punctatus (Bloch.). Fish were exposed to cupric chloride at the concentration of 10 ppb for 4 wk (28 d) in a static culture condition. Copper significantly (p < 0.001) increased the serum ceruloplasmin level and total iron-binding capacity. A significant (p < 0.05) increase in reduced glutathione level was recorded in all of the tissues. With regard to nonprotein thiols, copper decreased their level in the liver, but increased it in the gill. The protein-bound thiols remained unaltered except for an increase in the liver. Metallothionein (MT) induction was observed in liver only. Copper exposure had no significant effect on the ascorbic acid level and induced no lipid peroxidation over control values. It is suggested that by modulating the ceruloplasmin level, copper indirectly protects the fish, as it facilitates conversion of pro-oxidant iron to nonoxidant iron. It also induces an array of antioxidants that may be beneficial to fish in the case of oxidative stress resulting from chemical pollutants.     

Effect of selenium on lipids, lipid peroxidation, and sulfhydryl group in neuroendocrine centers of rats

The effects of various doses of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) were studied on the content of phospholipids, cholesterol, esterified fatty acids (EFA), gangliosides, thiobarbituric acid reactive substance (TBARS), and sulfhydryl group in neuroendocrine centers of male Wistar rats for 7 d. The lowest dose of Se (0.05 mg/kg) did not alter the above parameters significantly in neuroendocrine centers. The content of phospholipids was depleted significantly in the pituitary and depletion in the pineal was 80.22% with a 0.1-mg/kg dose of Se, but this dose elevated its level significantly in the hypothalamus. Conversely, a 0.2-mg/kg dose of selenium elevated the level of phospholipids significantly in the pituitary and hypothalamus, the elevation in the pineal was 70%. Selenium, 0.1 mg/kg, elevated the level of cholesterol in the pituitary but depleted its level in the pineal (56.8%) and hypothalamus (13.60%). Selenium, 0.2 mg/kg, elevated the level of cholesterol significantly in the hypothalamus but its level was not significant in the pituitary and pineal. The depletion of esterified fatty acid in the pituitary and pineal with doses of 0.1 and 0.2 mg/kg was significant in the pituitary, whereas its depletion in the pineal was 85.4% and 69.26%, respectively. Selenium, 0.1 and 0.2 mg/kg, depleted the level of gangliosides significantly and dose dependently in the pituitary but has elevated its level significantly and dose dependently in the hypothalamus. Its depletion in the pineal was 87.1% and 67.8% with the 0.1- and 0.2-mg/kg dose of selenium, respectively. Selenium, 0.1 mg/kg, increased the content of TBARS significantly in neuroendocrine centers and its elevation in the pineal was 703.8%. Selenium, 0.2 mg/kg, elevated its level in the pituitary and it was 126.9% in the pineal, but this dose depleted its level significantly in the hypothalamus. The content of the sulfhydryl group with a 0.1-mg/kg dose of selenite was depleted significantly in neuroendocrine centers and it was 55.9% in the pineal. Selenium, 0.2 mg/kg, depleted the level of the sulfhydryl group more significantly in the pituitary and pineal, but its elevation in hypothalamus was significant.     

The enteric toxins of Clostridium perfringens

The Gram-positive pathogen Clostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (~25–35 kDa) size, although lacking in sequence homology, and (2) they generally act by forming pores or channels in plasma membranes of host cells. These enteric toxins include C. perfringens enterotoxin (CPE), which is responsible for the symptoms of a common human food poisoning and acts by forming pores after interacting with intestinal tight junction proteins. Two other C. perfringens enteric toxins, -toxin (a bioterrorism select agent) and -toxin, cause veterinary enterotoxemias when absorbed from the intestines; - and -toxins then apparently act by forming oligomeric pores in intestinal or extra-intestinal target tissues. The action of a newly discovered C. perfringens enteric toxin, 2 toxin, has not yet been defined but precedent suggests it might also be a pore-former. Experience with other clostridial toxins certainly warrants continued research on these C. perfringens enteric toxins to develop their potential as therapeutic agents and tools for cellular biology.

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Insulin-like growth factor 1 stimulation of androgen receptor activity requires β(1A) integrins

Despite the findings that β1 integrins play a vital role in the regulation of cell proliferation and survival, the mechanisms through which they operate and lead to cancer progression remain elusive. Previously, our laboratory has shown that β(1A) integrins support insulin-like growth factor 1 (IGFI)-mediated mitogenic and transforming activities. Here, we report that β(1A) integrins regulate basal levels of IGF-IR, although they are not critical for maintaining cancer cell morphology. Upon transfection of β(1A) siRNA and consequent downregulation of IGF-IR, we show inhibition of anchorage-independent growth of prostate cancer cells, a function which is dependent on IGF-IR expression. In addition, we demonstrate that IGFI-mediated activation of androgen receptor (AR), known to occur in prostate cancer cells, requires expression of β(1A) integrins as evaluated by luciferase reporter assays and immunoblotting analysis. Since β(1A) integrin levels are increased by R1881 or dihydrotestosterone (DHT), our results imply that β(1A) integrins support an androgen-enhanced feedback loop that regulates the expression of IGF-IR. β(1A) integrins also regulate inducible levels of IGF-IR in cells stimulated by androgen or by a combination of androgen and IGFI, as evaluated by flow cytometric analysis and immunoblotting. Furthermore, upon transfection of β(1A) siRNA and consequent downregulation of IGF-IR, neither activation of AKT, an effector of IGF-IR, nor AR levels are affected. We conclude that β(1A) integrin expression is critical for maintaining the regulatory crosstalk between IGF-IR and AR.     

Antibacterial activity directed isolation of compounds from Onosma hispidum

The chemical investigation of the ethanolic extract of the root bark of Onosma hispidum following antibacterial activity directed isolation led to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) and 4-hydroxy-3-methoxy benzoic acid (vanillic acid) which have been reported for the first time in this species. In addition to these compounds, the crude ethanolic extract and methanol fraction exhibited substantial bioactivity against species of corynebacteria, enterococci, staphylococci and streptococci. Ferulic acid was found more bioactive (being relatively more hydrophobic) compared to vanillic acid.     

Inhibition of cell growth by K channel modulators is due to interference with agonist-induced Ca release

The effects of K⁺ channel modulators, tetraethylammonium, 4-aminopyridine and diazoxide, and high extracellular K⁺ on cell growth and agonist-induced intracellular Ca²⁺ mobilization were investigated. Two human brain tumour cell lines, U-373 MG astrocytoma and SK-N-MC neuroblastoma, were used as model cellular systems. K⁺ channel modulators and increased extracellular K⁺ concentration inhibited tumour cell growth in a dose-related fashion in both cell lines. In addition, agonist (carbachol or serum)-induced intracellular Ca²⁺ mobilization was also blocked by the pretreatment of growth-inhibitory concentrations of K⁺ channel modulators and high extracellular K⁺. Thus, these results suggest that K⁺ channel modulators are effective inhibitors of brain tumour cell growth and that their growth regulation may be due to the interference with the intracellular Ca²⁺ signalling mechanisms.     

The effect of insulin on glucose uptake in soleus muscle during hemorrhagic shock.

Hemorrhagic shock was produced by bleeding conscious rats to a mean arterial pressure of 40 mm Hg, which was maintained for 2 h. Basal glucose uptake by isolated soleus muscle from normal rats and rats subjected to hemorrhagic shock ('shock' muscles) increased with the increase ib medium glucose concentration. Uptake values were similar in both groups of muscles. This indicates that there were no alterations in the basal glucose carrier mechanism during shock. Whereas insulin (0.1 U/ml) stimulated glucose uptake in control muscles under aerobic as well as under anaerobic conditions, it had no stimulatory effect in 'shock' muscles under either environment. Maximal stimulation of glucose uptake in 'shock' muscles was observed at an insulin concentration of 0.2 U/ml. The ability of muscle to bind insulin was not altered during shock. The present experiments indicate that insulin responsiveness to tissues is altered in shock. This could be due to alterations in the insulin sensitivity of the glucose carrier mechanism during shock.