Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients

Context

Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.

Objective

The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.

Design and setting

A multi-centre, cross-sectional case-control study was performed.

Patients

Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.

Main outcome measures

Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells.

Results

Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O₂ consumption (P<0.05), mitochondrial membrane potential (P<0.01) and GSH levels (P<0.05), and an increase in ROS production (P<0.05) with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05), while the activity of mitochondrial complex I (P<0.001), but not that of complex III, was found to be inhibited in the same population.

Conclusions

Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.     

Activation by phosphate of yeast phosphofructokinase.

The activity of yeast phosphofructokinase assayed in vitro at physiological concentrations of known substrates and effectors is 100-fold lower than the glycolytic flux observed in vivo. Phosphate synergistically with AMP activates the enzyme to a level within the range of the physiological needs. The activation by phosphate is pH-dependent: the activation is 100-fold at pH 6.4 while no effect is observed at pH 7.5. The activation by AMP, phosphate, or both together is primarily due to changes in the affinity of the enzyme for fructose-6-P. Under conditions similar to those prevailing in glycolysing yeast (pH 6.4, 1 mM ATP, 10 mM NH4+) the apparent affinity constant for fructose-6-P (S0.5) decreases from 3 to 1.4 mM upon addition of 1 mM AMP or 10 mM phosphate; if both activators are present together, S0.5 is further decreased to 0.2 mM. In all cases the cooperativity toward fructose-6-P remains unchanged. These results are consistent with a model for phosphofructokinase where two conformations, with different affinities for fructose-6-P and ATP, will present the same affinity for AMP and phosphate. AMP would diminish the affinity for ATP at the regulatory site and phosphate would increase the affinity for fructose-6-P. The results obtained indicate that the activity of phosphofructokinase in the shift glycolysis-gluconeogenesis is mainly regulated by changes in the concentration of fructose-6-P.     

The effect of pre-eclamptic umbilical cord serum on fibroblast division in culture

Edema, proteinuria, hypertension (EPH-gestosis), most commonly termed as pre-eclampsia, is the most common pregnancy-associated pathological syndrome. It is accompanied by a thorough remodelling of extracellular matrix in the umbilical cord tissues. It is commonly known that the presence of serum in culture medium strongly stimulates many functions of cells cultured in vitro. It was decided to check how the pre-eclamptic serum affects the fibroblast division in culture. Ki-67 is a protein present in proliferating cells and can be detected during all phases of the cell cycle (G1, S, G2/M) but not in resting (G0) cells. PCNA (proliferating cell nuclear antigen) is an intranuclear polypeptide whose synthesis rate is at its maximum during the S-phase of the cell cycle. The expression of Ki-67 and PCNA was measured by immunocytochemical methods and biosynthesis of DNA was evaluated by [14C]-thymidine incorporation. The activity of pre-eclamptic umbilical cord serum (UC-serum) was found to be distinctly lower in comparison to control one. The expression of Ki and PCNA in fibroblast cultures treated with pre-eclamptic serum was also distinctly lower. Also the incorporation of [14C]-thymidine to DNA was lower than in the cultures treated with control UC-serum. It may by concluded that pre-eclampsia reduces the mitogenic activity of the umbilical cord serum.     

Association of multiple drug resistance-1 gene polymorphism with multiple drug resistance in breast cancer patients from an ethnic Saudi Arabian population

Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p < 0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia.     

Middle Palaeolithic and Neolithic Occupations around Mundafan Palaeolake,Saudi Arabia: Implications for Climate Change and Human Dispersals

The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub’ al-Khali (the ‘Empty Quarter’), the world’s largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub’ al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources.     

Phosphate starvation response controls genes required to synthesize the phosphate analog arsenate

Environmental arsenic poisoning affects roughly 200 million people worldwide. The toxicity and mobility of arsenic in the environment is significantly influenced by microbial redox reactions, with arsenite (As^III) being more toxic than arsenate (As^V). Microbial oxidation of As^III to As^V is known to be regulated by the AioXSR signal transduction system and viewed to function for detoxification or energy generation. Here, we show that As^III oxidation is ultimately regulated by the phosphate starvation response (PSR), requiring the sensor kinase PhoR for expression of the As^III oxidase structural genes aioBA. The PhoRB and AioSR signal transduction systems are capable of transphosphorylation cross‐talk, closely integrating As^III oxidation with the PSR. Further, under PSR conditions, As^V significantly extends bacterial growth and accumulates in the lipid fraction to the apparent exclusion of phosphorus. This could spare phosphorus for nucleic acid synthesis or triphosphate metabolism wherein unstable arsenic esters are not tolerated, thereby enhancing cell survival potential. We conclude that As^III oxidation is logically part of the bacterial PSR, enabling the synthesis of the phosphate analog As^V to replace phosphorus in specific biomolecules or to synthesize other molecules capable of a similar function, although not for total replacement of cellular phosphate.     

Effects of irrigation and air humidity preconditioning on water relations, growth and survival of Rosmarinus officinalis plants during and after transplanting

The effect of different irrigation and air humidity conditioning treatments on the morphological and physiological responses of Rosmarinus officinalis in nursery conditions was investigated in order to evaluate the degree of hardening resulting from these conditions. Rosmarinus officinalis seedlings were pot-grown during 4 months in two greenhouses (nursery period), in which two irrigation treatments were used (control and deficit). In one of these greenhouses, air humidity was controlled using a dehumidifying system (low humidity), in the other greenhouse the air conditions were not artificially modified (control humidity). After the nursery period, the plants of all treatments were transplanted and well watered (100% water holding capacity for 1 month, transplanting period). After this period, they received no water (establishment period). At the end of the nursery period it was seen that deficit irrigation had altered the morphology of the R. officinalis plants by reducing plant height, stem diameter, leaf area, total dry weight, and root length, while humidity influenced the parameters related with plant water relations. Low air humidity and deficit irrigation-induced tissue dehydration and lower stomatal conductance values (gs). The plants subjected to deficit irrigation developed leaf osmotic adjustment, which was maintained during the transplanting period. At that time, the plants that had been exposed to deficit irrigation and low humidity showed efficient stomatal regulation (lower gs values). After transplanting and during the establishment period, these plants showed a better water status (higher psil and gs values). Their post-planting survival rate improved as a result of acclimation processes.     

Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor in tuberculosis

Several genes encoding for different cytokines may play crucial roles in host susceptibility to tuberculosis (TB), since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphism. The association of the cytokine gene polymorphisms with the development of TB was investigated in this study. DNA samples were obtained from a Turkish population of 81 patients with the different clinical forms of TB, and 50 healthy control subjects. All genotyping (IL-6, IL-10, IFN-gamma, TGF-beta and TNF-alpha) experiments were performed using sequence-specific primers PCR (PCR-SSP). Analysis of allele frequencies showed that IL-10 -1082 G allele frequency was significantly more common in TB patients than healthy controls (37.7% vs 23.0%, p: 0.014). No statistically significant differences were observed between the different clinical forms of the disease. These results suggest that the polymorphisms in IL-10 gene may affect susceptibility to TB and increase risk of developing the disease. To confirm the biological significance of our results, further studies should be performed on other population groups.     

Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells

Biochemical Genetics - The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6&nbsp;days from...