Vitamin D is a prooxidant in breast cancer cells.

The anticancer activity of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], is associated with inhibition of cell cycle progression, induction of differentiation, and apoptosis. In addition, 1,25(OH)2D3 augments the activity of anticancer agents that induce excessive reactive oxygen species generation in their target cells. This study aimed to find out whether 1,25(OH)2D3, acting as a single agent, is a prooxidant in cancer cells. The ratio between oxidized and reduced glulathione and the oxidation-dependent inactivation of glyceraldehyde-3phosphate dehydrogenase (GAPDH) are considered independent markers of cellular reactive oxygen species homeostasis and redox state. Treatment of MCF-7 breast cancer cells with 1,25(OH)2D3 (10-100 nM for 24-48 h) brought about a maximal increase of 41+/-13% (mean +/- SE) in the oxidized/reduced glutathione ratio without affecting total glutathione levels. The in situ activity of glutathione peroxidase and catalase were not affected by 1,25(OH)2D3, as assessed by the rate of H2O2 degradation by MCF-7 cell cultures. Neither did treatment with 1,25(OH)2D3 affect the levels of glutathione reductase or glutathione S-transferase as assayed in cell extracts. The hormone did not affect overall glutathione consumption and efflux as reflected in the rate of decline of total cellular glutathione after inhibition of its synthesis by buthionine sulfoximine. The extent of reversible oxidation-dependent inactivation of GAPDH in situ was determined by comparing the enzyme activity before and after reduction of cell extracts with DTT. The oxidized fraction was 0.13+/-0.02 of total GAPDH in control cultures and increased by 56+/-5.3% after treatment with 1,25(OH)2D3, which did not affect the total reduced enzyme activity. Treatment with 1,25(OH)2D3 resulted in a approximately 40% increase in glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the generation of NADPH. This enzyme is induced in response to various modes of oxidative challenge in mammalian cells. Taken together, these findings indicate that 1,25(OH)2D3 causes an increase in the overall cellular redox potential that could translate into modulation of redox-sensitive enzymes and transcription factors that regulate cell cycle progression, differentiation, and apoptosis.

Distributed neural network underlying musical sight-reading and keyboard performance.

Music, like other forms of expression, requires specific skills for its production, and the organization and representation of these skills in the human brain are not well understood. With the use of positron emission tomography and magnetic resonance imaging, the functional neuroanatomy of musical sight-reading and keyboard performance was studied in ten professional pianists. Reading musical notations and translating these notations into movement patterns on a keyboard resulted in activation of cortical areas distinct from, but adjacent to, those underlying similar verbal operations. These findings help explain why brain damage in musicians may or may not affect both verbal and musical functions depending on the size and location of the damaged area.

Positron emission tomography study of letter and object processing: empirical findings and methodological considerations.

The study of functional-anatomical correlations of higher-order cognitive processing has benefited from recent advances in brain imaging techniques such as positron emission tomography (PET) measurements of regional cerebral blood flow (CBF). Comparisons of CBF changes by paired image subtraction provide the opportunity to isolate cerebral areas participating in the realization of the processes that differentiate two tasks. However, the subtraction method is based on assumptions that are not entirely compatible with cerebral cognitive processing, and the derived pattern of activation specifically associated with the processes that differentiate two tasks is relative to the activation associated with the subtracted task and may therefore vary as a function of the processes actually performed in this subtracted task. To examine the implications of this procedure, a PET study with the 15O water bolus technique was carried out on normal adults. Subjects performed three tasks that made nonoverlapping cognitive processing demands: a semantic categorization of visual objects, a spatial discrimination of visually presented letters, and a phonological decision on visually presented single letters. Each task produced distinct patterns of activation consistent with evidence from neurological patients, specifically in the left occipital cortex in the semantic categorization of objects, in the parietal cortex of both hemispheres in the letter-spatial task, and in the left frontal and superior temporal cortex in the letter-sound task. However, the comparisons between the two letter tasks did not result in the expected CBF changes even though these two tasks make distinct processing requirements and are dissociable by brain injury. In addition, the phonological task resulted in activation of areas of the frontal cortex that earlier PET studies had identified as participating in semantic operations, whereas letters have no semantic property. These results suggest that the interpretation of patterns of activation is confronted with difficulties due to the automatic, and uncontrolled, processing of verbal stimuli that raises the threshold for significant CBF changes between two conditions that use the same stimuli but different task demands.