Homocysteine, vitamin determinants and neurological diseases.

This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma

NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells

<p>Abstract</p> <p>Background</p> <p>Perinatal exposure to hyperhomocysteinemia might disturb neurogenesis during brain development and growth. Also, high levels of homocysteine trigger neurodegeneration in several experimental models. However, the putative mechanisms of homocysteine-induced toxicity in the developing nervous system have poorly been elucidated. This study was aimed to investigate homocysteine effects in undifferentiated neuroblastoma cells, Neuro2a.</p> <p>Results</p> <p>A 4 h exposure to homocysteine in a concentration range of 10–100 μM did not affect cell viability and ROS production in Neuro2a cell cultures. Instead, ROS levels were increased by two-three folds in cells treated with 250 μM and 500 μM homocysteine, respectively, in comparison with control cells. Also, the highest homocysteine dose significantly reduced the viable cell number by 40%. Notably, the treatment with homocysteine (250 μM–500 μM) in the presence of antioxidants, such as N-acetylcysteine and IRFI 016, a synthetic α-tocopherol analogue, recovered cell viability and significantly reduced homocysteine-evoked increases in ROS production. Moreover, antioxidants, particularly IRFI 016, were able to counteract NF-κB activation induced by 250 μM homocysteine.</p> <p>Cell treatment with 250 μM homocysteine also triggered the onset of apoptosis, as demonstrated by the increased expression of early apoptotic markers such as Bax, caspase-3 and p53. In contrast, Bcl2 expression was not affected by homocysteine exposure. Interestingly, the specific inhibition of NF-κB nuclear translocation by the synthetic peptide SN50 was able to almost completely suppress the homocysteine-evoked rises in pro-apoptotic protein expression as well as in caspase-3 activity. Further, also IRFI 016 and N-acetylcysteine were able to significantly reduce caspase-3 activation induced by homocysteine treatment.</p> <p>Conclusion</p> <p>These observations suggest an involvement of redox state alterations and activated NF-κB in apoptosis onset triggered by homocysteine in neuroblastoma cells Neuro2a. However, further investigations are needed to characterize molecular events involved in the NF-κB activation induced by homocysteine.</p

Electrophysiological actions of zonisamide on striatal neurons: Selective neuroprotection against complex I mitochondrial dysfunction

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Monitoring of cardiovascular risk factors in competitive athletes

It is well known that physical activity can improve cardiovascular risk factors, but it is also true that strenuous activity may result detrimental for the athlete health. Among the emerging markers of cardiovascular risk, plasma homocysteine (Hcy) plays a prominent role, since it has been shown its significant increase in competitive athletes. Some research has concluded that Hcy levels may be influenced by the duration, intensity and type of exercise, whereas other studies have identified lifestyle factors, such as smoking, eating habits, alcohol consumption, age, elevated blood pressure and genetic factors, as factors that contribute to increased plasma concentrations of Hcy. Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) (677C/T, 1298A/C) are reported to modulate homocysteine levels. The aim of this work was to identify a genetic profile of risk for cardiovascular disease in two populations of competitive athletes, football players (n = 19) and those engaged in athletics (n=37). The distribution of MTHFR A1298C and C677T polymorphisms was examined by Real-time PCR allelic discrimination on genomic DNA isolated from lymphocytes of whole peripheral blood. The serum levels of Hcy were determined by HPLC method, while vitamin B12 and folate by RIA technique. The data showed that 50% of the subjects in both groups are carrier of MTHFR C677T polymorphism either in heterozygous or homozygous state. In addition, all subjects had mild hyperhomocysteinemia (13-27 micromol/L). The highest mean levels of Hcy were recorded in the football players, and the differences compared to those engaged in athletics were very significant (21.8 ± 11.6 vs. 13.5 ± 6.6, p &lt;0.05). The increase of Hcy could be ascribed mainly to the diet style of the recruited subjects, characterized by a high consumption of red meat and very low intake of B vitamins. Moreover, this increase may also be explained in relation to the type of exercise required in football, that is considered an intermittent intensity sport. The preliminary results of this study suggest that screening for the MTHFR variants C677T and A1298C should be included in the panel of screening for cardiovascular risk in competitive athletes

cellular apoptosis mitochondrial function and confers resistance to The arginine metabolite agmatine protects

is dedicated to innovative approaches to the study of cell and molecular physiology. It is published 12 times AJP -Cell Physiolog

Health Risks of Hypovitaminosis D: A Review of New Molecular Insights

Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich food, are likely involved in the etiology of a dramatic reduction of vitamin D circulating levels. The insufficiency/deficiency of vitamin D has long been known for its association with osteoporosis and rickets. However, in the last few decades it has become a serious public health concern since it has been shown to be independently associated with various chronic pathological conditions such as cancer, coronary heart disease, neurological diseases, type II diabetes, autoimmune diseases, depression, with various inflammatory disorders, and with increased risk for all-cause mortality in the general population. Prevention strategies for these disorders have recently involved supplementation with either vitamin D2 or vitamin D3 or their analogs at required daily doses and tolerable upper-limit levels. This review will focus on the emerging evidence about non-classical biological functions of vitamin D in various disorders

Dietary Intake and Genetic Background Influence Vitamin Needs during Pregnancy

Numerous approaches demonstrate how nutritional intake can be sufficient to ensure the necessary supply of vitamins. However, it is evident that not all vitamins are contained in all foods, so it is necessary either to combine different food groups or to use a vitamin supplement to be well-fed. During pregnancy, deficiencies are often exacerbated due to increased energy and nutritional demands, causing adverse outcomes in mother and child. Micronutrient supplementation could lead to optimal pregnancy outcomes being essential for proper metabolic activities that are involved in tissue growth and functioning in the developing fetus. In order to establish adequate vitamin supplementation, various conditions should be considered, such as metabolism, nutrition and genetic elements. This review accurately evaluated vitamin requirements and possible toxic effects during pregnancy. Much attention was given to investigate the mechanisms of cell response and risk assessment of practical applications to improve quality of life. Importantly, genetic studies suggest that common allelic variants and polymorphisms may play an important role in vitamin metabolism during pregnancy. Changes in gene expression of different proteins involved in micronutrients’ metabolism may influence the physiological needs of the pregnant woman

Transglutaminase 2 Up-Regulation Is Associated with Inflammatory Response in PBMC from Healthy Subjects with Hypovitaminosis D

Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-&#954;B signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-&#945; mRNA levels in PBMC of recruited patients. The mRNA levels of TG2 and TNF-&#945; were higher in PBMC of subjects having hypovitaminosis D, namely plasma 25(OH)vitamin D3 levels lower than 50 nmol/L, than in those with normal vitamin D levels. Moreover, NF-&#954;B up-regulation and nuclear translocation were detected, concomitantly with TG2 as well as TNF-&#945; increased expression, in PBMC of vitamin D-deficient subjects. The present findings confirm that an increase in TG2 expression exacerbates the activation of NF-&#954;B and the production of pro-inflammatory cytokines, and suggest a link between vitamin D deficiency, TG2 up-regulation, and inflammation