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Thiamine and Oxidants Interact to Modify Cellular Calcium Stores

Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamaroneck Ave, White Plains, NY 10605, USA.
Neurochemical Research (Impact Factor: 2.55). 12/2010; 35(12):2107-16. DOI: 10.1007/s11064-010-0242-z
Source: PubMed

ABSTRACT Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer's disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3-morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes.

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    • "Thiamine helps to promote healthy nerves, improves mood, strengthens the heart, and decreases heartburn (Fardet 2010). It also is an antioxidant (Huang et al. 2010; Lukienko et al. 2000). A cross-sectional study of 2,900 Australian men and women, 49 years of age and older, found that those in the highest quintile of thiamine intake were 40% less likely to have nuclear cataracts than those in the lowest quintile (Cumming et al. 2000). "
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    ABSTRACT: Thiamine pyrophosphate (vitamin B1) is an essential nutrient in the human diet, and is often referred as the energy vitamin. Potato contains modest amounts of thiamine. However, the genetic variation of thiamine concentrations in potato has never been investigated. In this study, we determined thiamine concentrations in freshly-harvested unpeeled tubers of 54 potato clones, the majority of them originating from the Pacific Northwest Potato Development Program. Tubers from 39 clones were collected from four different environmental conditions. Thiamine concentrations ranged from 292 to 1,317ngg−1 fresh weight, which gives a good estimate of the genetic variation available in Solanum tuberosum ssp. tuberosum. Thirteen clones/varieties contained >685ngg−1 fresh weight and four had >800ngg−1 fresh weight over multiple harvests, indicating that these genotypes would contribute a significant amount of thiamine in the diet (>10% of the Recommended Daily Allowance based on a 175- or 150-g serving, respectively). Broad-sense heritability for thiamine content was calculated as 0.49 with a 95% confidence interval of 0.21–0.72, suggesting that genetic variation accounted for about 50% of the observed variation. There were significant clone and clone x environment effects. After accounting for environmental variation, 25 clones were unstable across environments. Tubers harvested at a mature stage late in the growing season had higher amounts of thiamine than tubers harvested at a young stage early in the season. Storage at cold temperature did not lead to significant thiamine loss; instead, thiamine concentrations slightly increased during storage in some genotypes. These results suggest that increasing the concentration of thiamine in potato is feasible and that all potato varieties may oneday be a significant source of thiamine in the human diet. La tiamina-pirofosfato (vitamin B1) es un nutriente esencial en la dieta humana, y a menudo se refiere a ella como la vitamina de la energía. La papa contiene cantidades modestas de tiamina. No obstante, la variación genética de las concentraciones de tiamina en papa nunca se ha investigado. En este estudio determinamos las concentraciones de tiamina en tubérculos sin pelar recién cosechados de cincuenta y cuatro clones de papa, la mayoría de ellos se originaron del Programa de Desarrollo de Papa del Pacífico-Noroeste. Se colectaron tubérculos de treinta y nueve clones de cuatro diferentes condiciones ambientales. Las concentraciones de tiamina variaron de292 a 1,317ngg-1 de peso fresco, lo que da una buena estimación de la variación genética disponible en Solanum tuberosum ssp. Tuberosum. Trece clones/variedades contenían >685ngg-1 de peso fresco y cuatro tuvieron >800ngg-1 de peso fresco en múltiples cosechas, indicando que estos genotipos contribuirían con una cantidad significativa de tiamina en la dieta (>10% de la cantidad recomendada diariamente basada en un 175 o 150g por porción, respectivamente). Se calculó la heredabilidad en amplio sentido para el contenido de tiamina como 0.49 con un intervalo de confianza de 95% de 0.21–0.72, lo que sugiere que la variación genética contó para cerca de 50% de la variación observada. Hubo efectos significativos de clon y de clon x ambiente. Después de contabilizar para la variación por el ambiente, 25 clones fueron inestables entre ambientes. Los tubérculos cosechados en un estado maduro tarde en el ciclo de cultivo tuvieron cantidades más altas de tiamina que los tubérculos cosechados en un estado joven temprano en el ciclo. El almacenamiento a baja temperatura no condujo a pérdida significativa de tiamina; más bien, las concentraciones de tiamina aumentaron ligeramente durante el almacenamiento en algunos genotipos. Estos resultados sugieren que es posible el aumento en la concentración de tiamina y que todas las variedades de papa pudieran algún día ser una fuente significativa de tiamina en la dieta humana. Keywords Solanum tuberosum –Genotype x environment interactions–Thiamine pyrophosphate
    American Journal of Potato Research 07/2011; 88(4):374-385. DOI:10.1007/s12230-011-9203-6 · 0.95 Impact Factor
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    • "A major cause of ER stress is the perturbation of calcium homeostasis [15-17]. Thiamine selectively diminished the reactive nitrogen species (RNS) and capacitative calcium entry (CCE) in the endoplasmic reticulum of fibroblasts [45]. Therefore, it is likely that TD-induced ER stress in neurons results from alterations in [Ca2+]i. "
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    ABSTRACT: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons. TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated by RNA editing at the Q/R site. Edited GluR2 (R) subunits form Ca2+-impermeable channels, whereas unedited GluR2 (Q) channels are permeable to Ca2+ flow. TD inhibited Q/R editing of GluR2 and increased the ratio of unedited GluR2. The Q/R editing of GluR2 is mediated by adenosine deaminase acting on RNA 2 (ADAR2). TD selectively decreased ADAR2 expression and its self-editing ability without affecting ADAR1 in cultured neurons and in the brain tissue. Over-expression of ADAR2 reduced AMPA-mediated rise of [Ca2+]i and protected cortical neurons against TD-induced cytotoxicity, whereas down-regulation of ADAR2 increased AMPA-elicited Ca2+ influx and exacerbated TD-induced death of cortical neurons. Our findings suggest that TD-induced neuronal damage may be mediated by the modulation of ADAR2-dependent RNA Editing of GluR2.
    Molecular Neurodegeneration 11/2010; 5(1):54. DOI:10.1186/1750-1326-5-54 · 5.29 Impact Factor
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