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Decrease in Ca2+-ATPase activity in the brain plasma membrane of rats with increasing age: involvement of brain
1Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
International Journal of Molecular Medicine
|March 20, 2001
Summary
Aging significantly reduces brain plasma membrane Ca(2+)-ATPase activity in rats, leading to increased brain calcium levels. This age-related decline in enzyme function may explain calcium accumulation in the aging brain.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Calcium homeostasis is crucial for brain function.
- Age-related changes in enzyme activity can impact cellular processes.
- Ca(2+)-ATPase plays a key role in regulating intracellular calcium levels.
Purpose of the Study:
- To investigate the effect of aging on Ca(2+)-ATPase activity in rat brain plasma membranes.
- To explore the role of thiol groups and signaling factors in age-related changes of Ca(2+)-ATPase.
- To understand the cellular mechanisms underlying age-associated calcium accumulation in the brain.
Main Methods:
- Measurement of Ca(2+)-ATPase activity in brain plasma membranes from young and aged rats.
- Assessment of the effects of thiol-modifying (N-ethylmaleimide) and protecting (dithiothreitol) reagents.
- Investigation of the influence of signaling molecules like dibutyryl cyclic AMP and inositol 1, 4, 5-trisphosphate.
Main Results:
- Aged rats exhibited significantly higher brain calcium content and reduced Ca(2+)-ATPase activity compared to young rats.
- Thiol (SH)-groups were identified as active sites of Ca(2+)-ATPase, unaffected by aging.
- The inhibitory effects of cyclic AMP and inositol trisphosphate on Ca(2+)-ATPase were diminished in aged rats, suggesting weakened signaling pathways.
Conclusions:
- Aging leads to a significant decrease in brain plasma membrane Ca(2+)-ATPase activity.
- The impaired enzyme activity contributes to calcium accumulation in the aging brain.
- Age-related decline in responsiveness to signaling factors may underlie altered calcium regulation.