Regulation of Bcl-2 family proteins by posttranslational modifications

Like many proteins, function and abundance of Bcl-2 family proteins are influenced by posttranslational modifications. These modifications include phosphorylation, proteolytic cleavage, ubiquitination, and proteosomal degradation. These modifications, depending on cellular context and the proteins involved, can result either in a promotion of inhibition of apoptosis. Many of these modifications are governed by the activity of enzymes. As modulation of enzymatic activity can be achieved fairly efficiently using small molecules, understanding the effects of posttranslational modifications may allow for the therapeutic inhibition or promotion of apoptosis.     

The Effects of Melatonin on Transcriptional Profile of Unfolded Protein Response Genes Under Endoplasmic Reticulum Stress in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>

When the load of secretory pathway is increased or folding capacity in the endoplasmic reticulum (ER) is insufficient, unfolded proteins might accumulate in ER lumen causing a phenomenon called ER stress. During ER stress, normal cell functions are suppressed and unfolded protein response (UPR) is induced. Studies in animal systems suggest that melatonin alleviates the detrimental effects of ER stress; however, there is no study in plants in this respect. Hence, in this study, we investigated the possible role of melatonin on alleviation of ER stress in model plant Arabidopsis thaliana. Tunicamycin (Tm) was used to specifically induce ER stress. Melatonin treatment (10 and 25 μM but not 1 μM) increased root growth under Tm treatment, but it did not reach control levels. ER stress induced the expressions of ER stress sensor/transducer genes, ER chaperones and folding helper genes, ER-associated degradation (ERAD) genes, and ER stress-associated apoptosis genes in roots and shoots (a total of 16 genes). Among them, the expressions of ER stress sensor/transducer bZIP17, bZIP28, IRE1A, IRE1B, ERAD-related SEL1, and apoptosis genes AGB1 were decreased back to control levels with 25 μM melatonin under ER stress in roots. Moreover, Tm?+?melatonin treatments decreased the expressions of these genes when compared to only Tm-treated plants. Downregulation of UPR components with increased concentrations of melatonin under Tm treatment demonstrated that melatonin alleviated the detrimental effects of ER stress.     

Effect of zinc deficiency and supplementation on lipid peroxidation of renal tissue in ovariectomized rats

The aim of this study was to investigate how zinc deficiency and supplementation affects lipid peroxidation in the renal tissue in ovariectomized rats. Four study groups were formed with 10 Spraque-Dawley rats each. Two of the groups served as normal and ovariectomized controls; the other two were ovariectomized rats that were zinc deficient and zinc supplemented, respectively. The zinc-deficient ovariectomized rats showed greater renal and plasma lipid peroxidation, as indicated by higher malondialdehyde levels than all other groups (p<0.05). These values were higher in the ovariectomized controls than those of the normal controls and of the ovariectomized, zinc-supplemented groups (p<0.05), which, in, turn, showed no significant differences of their respective renal and plasma malondialdehyde values. The renal and erythrocyte glutathione levels in the zinc-supplemented rats were higher than those in all other groups (p<0.05). The zinc-deficient group had the lowest renal and erythrocyte glutathione levels (p<0.05). The renal tissue zinc levels in the ovariectomized rats were higher than those in the zinc-deficient animals, but lower than in the normal controls and zincsupplemented rats (p<0.05). The zinc-supplemented animals had the highest renal tissue zinc levels (p<0.05). The results of this study suggest that zinc deficiency increases renal tissue damage in ovariectomized rats and that zinc supplementation can be used to prevent this condition.     

Interactions between nebulin-like motifs and thin filament regulatory proteins

Nebulin (600-900 kDa) and nebulette (107-109 kDa) are two homologous thin filament-associated proteins in skeletal and cardiac muscles, respectively. Both proteins are capped with a unique region at the amino terminus as well as a serine-rich linker domain and SH3 domains at the COOH terminus. Their significant size difference is attributed to the length of the central region wherein both proteins are primarily composed of approximately 35 amino acid repeats termed nebulin-like repeats or motifs. These motifs are marked by a conserved SXXXY sequence and high affinity binding to F-actin. To further characterize the effects that nebulin-like proteins may have on the striated muscle thin filament, we have cloned, expressed, and purified a five-motif chicken nebulette fragment and tested its interaction with the thin filament regulatory proteins. Both tropomyosin and troponin T individually bound the nebulette fragment, although the affinity of this interaction was significantly increased when tropomyosin-troponin T was tested as a binary complex. The addition of troponin I to the tropomyosin-troponin T complex decreased the binding to the nebulette fragment, indicating an involvement of the conserved T2 region of troponin T in this interaction. F-actin cosedimentation demonstrated that the nebulette fragment was able to significantly increase the affinity of the tropomyosin-troponin assembly for F-actin. The relationships provide a means for nebulin-like motifs to participate in the allosteric regulation of striated muscle contraction.     

Lipid peroxidation in ovariectomized and pinealectomized rats: the effects of estradiol and progesterone supplementation

In the present study, we investigated the effect of estradiol and progesterone supplementation on oxidant and antioxidant parameters of renal tissue in ovariectomized and pinealectomized rats. The study was carried out on 36 adult, Sprague-Dawley strain female rats, 6 months of age and weighing 200-250 g. The rats were divided into six groups, each group included six rats: Group 1: Sham-ovariectomized (Sham-Ovx); Group 2: Ovariectomized (Ovx); Group 3: Ovx and estradiol (E) and progesterone (P) supplemented (Ovx+E-P); Group 4: Ovariectomized and sham pinealectomy (Ovx+sham Pnx); Group 5: Ovariectomized+Pinealectomized (Ovx+Pnx); Group 6: Ovariectomized+Pinealectomized+Hormone Supplemented group (Ovx+Pnx+E-P). The levels of malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were analysed in renal tissues of rats. The highest and the lowest levels of MDA were determined in Groups 5 and 1 respectively (p < 0.001). However, GSH and GSH-Px levels demonstrated statistically important decreases in groups 2, 4, 5 (p < 0.001). The findings of this study demonstrate that ovariectomy leads to oxidative damage in renal tissue. Pinealectomy in addition to ovariectomy greatly increases the oxidative damage. However, female sex hormones supplementations to the Ovx and/or Ovx+Pnx rats protected against lipid peroxidation by activating the antioxidant system.     

Autologous rabbit adipose tissue-derived mesenchymal stromal cells for the treatment of bone injuries with distraction osteogenesis

Background aimsAdipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects.MethodsBone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs.ResultsRadiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits.ConclusionsThese data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects.     

Effect of Selenium Supplementation on Lipid Peroxidation,Antioxidant Enzymes,and Lactate Levels in Rats Immediately After Acute Swimming Exercise

The present study aims to evaluate the effect of selenium supplementation on lipid peroxidation and lactate levels in rats subjected to acute swimming exercise. Thirty-two adult male rats of Sprague–Dawley type were divided into four groups. Group 1, control; group 2, selenium-supplemented; group 3, swimming control; group 4, selenium-supplemented swimming group. The animals in groups 2 and 4 were supplemented with (i.p.) 6 mg/kg/day sodium selenite for 4 weeks. The blood samples taken from the animals by decapitation method were analyzed in terms of erythrocyte-reduced glutathione (GSH), serum glutathione peroxidase (GPx) and superoxide dismutase (SOD), and plasma malondialdehyde (MDA) and lactate using the colorimetric method, and serum selenium values using an atomic emission device. In the study, the highest MDA and lactate values were found in group 3, while the highest GSH, GPx and SOD values were obtained in group 4 (p < 0,001). Group 2 had the highest and group 3 had the lowest selenium levels (p < 0,001). Results of the study indicate that the increase in free radical production and lactate levels due to acute swimming exercise in rats might be offset by selenium supplementation. Selenium supplementation may be important in that it supports the antioxidant system in physical activity.     

The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study

Background

Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis.

Findings

Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less [³H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro.

Conclusions

These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis.