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: 2.59). 12/2010; 35(12):2107-16. DOI: 10.1007/s11064-010-0242-z
Source: PubMed


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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    ABSTRACT: Thiamin is an essential nutrient in the human diet. Severe thiamin deficiency leads to beriberi, a lethal disease which is common in developing countries. Thiamin biofortification of staple food crops is a possible strategy to alleviate thiamin deficiency-related diseases. In plants, thiamin plays a role in the response to abiotic and biotic stresses, and data from the literature suggest that boosting thiamin content could increase resistance to stresses. Here, we tested an engineering strategy to increase thiamin content in Arabidopsis. Thiamin is composed of a thiazole ring linked to a pyrimidine ring by a methylene bridge. THI1 and THIC are the first committed steps in the synthesis of the thiazole and pyrimidine moieties, respectively. Arabidopsis plants were transformed with a vector containing the THI1 coding sequence under the control of a constitutive promoter. Total thiamin leaf content in THI1 plants was up ~2-fold compared to the wild-type. THI1-overexpressing lines were then crossed with preexisting THIC-overexpressing lines ([Bocobza et al. (2013) Orchestration of Thiamin Biosynthesis and Central Metabolism by Combined Action of the Thiamin Pyrophosphate Riboswitch and the Circadian Clock in Arabidopsis. Plant Cell 25:288-307]). Resulting THI1 x THIC plants accumulated up to 3.4- and 2.6-fold more total thiamin than wild-type plants in leaf and seeds, respectively. After inoculation with Pseudomonas syringae, THI1 x THIC plants had lower populations than the wild-type control. However, THI1 x THIC plants subjected to various abiotic stresses did not show any visible or biochemical changes compared to the wild-type. We discuss the impact of engineering thiamin biosynthesis on plants nutritional value and resistance to biotic and abiotic stresses.
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    • "On the contrary, the B-complex vitamins may contribute to cellular repair by acting on cellular membrane lesions caused by free radicals (Huang et al. 2010). As such, the B-complex vitamins and vitamin E present in the vitamin complex probably represent the molecules responsible for the reduction in the phospholipase activity observed in our work, once low inhibition was observed for ascorbic acid, separately. "
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    ABSTRACT: Context: Natural compounds have been widely studied with the aim of complementing antiophidic serum therapy. Objective: The present study evaluated the inhibitory potential of ascorbic acid and a vitamin complex, composed of ascorbic acid, vitamin E, and all the B-complex vitamins, on the biological activities induced by snake venoms. Material and methods: The effect of vitamins was evaluated on the phospholipase, proteolytic, coagulant, and fibrinogenolytic activities induced by Bothrops moojeni (Viperidae), B. jararacussu, and B. alternatus snake venoms, and the hemagglutinating activity induced by B. jararacussu venom. Results: The vitamin complex (1:5 and 1:10 ratios) totally inhibited the fibrinogenolytic activity and partially the phospholipase activity and proteolytic activity on azocasein induced by the evaluated venoms. Significant inhibition was observed in the coagulation of human plasma induced by venoms from B. alternatus (1:2.5 and 1:5, to vitamin complex and ascorbic acid) and B. moojeni (1:2.5 and 1:5, to vitamin complex and ascorbic acid). Ascorbic acid inhibited 100% of the proteolytic activities of B. moojeni and B. alternatus on azocasein, at 1:10 ratio, the effects of all the venoms on fibrinogen, the hemagglutinating activity of B. jararacussu venom, and also extended the plasma coagulation time induced by all venoms analyzed. Discussion and conclusion: The vitamins analyzed showed relevant in vitro inhibitory potential over the activities induced by Bothrops venoms, suggesting their interaction with toxins belonging to the phospholipase A2, protease, and lectin classes. The results can aid further research in clarifying the possible mechanisms of interaction between vitamins and snake enzymes.
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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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