Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Change in calcium response was studied to clarify the pathological process of Alzheimer's disease (AD). Cultured fibroblasts from patients with familial Alzheimer's disease (FAD; n = 6), sporadic Alzheimer's disease (SAD; n = 4), and age-matched healthy control subjects (n = 4) were studied with an ACAS Interactive Laser Cytometer (ACAS-470). Fibroblasts from two independent families with FAD (OS-1, and OS-2 families) showed a suppressed calcium response after stimulation by 100 nM bradykinin (BK) 100 nM vasopressin (VP) or 10% FCS in Ca(2+)-free condition compared with control fibroblasts at 48 h after plating. However, on the 7th day after plating, the abnormal calcium response was no longer observed. The height of the calcium peak showed periodic variation, indicating a relationship of calcium response with the cell cycle. When fibroblasts from OS-1 and OS-2 families were arrested in S phase, they showed a significantly suppressed calcium peak after BK stimulation. However, when those fibroblasts were arrested in other phases, they showed the same calcium peak as the other cells. The suppression of calcium response in S phase was indistinguishable from the calcium suppression induced by A23187 administration. Since Hardy type mutation on amyloid precursor protein gene is found in the OS-1 family, the observed abnormalities in calcium response might be related with pathological processing of amyloid precursor protein in AD. The reported abnormal calcium response, which is observed most obviously in fibroblasts in S phase, may indicate participation of the cell-cycle-dependent process in the pathology of AD.
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PMID:Cell-cycle-dependent abnormal calcium response in fibroblasts from patients with familial Alzheimer's disease. 772 21

In the human keratinocyte cell line HaCaT, reactive oxygen species (ROS) were generated in a dose- and time-dependent manner in response to epidermal growth factor (EGF), bradykinin, thapsigargin, and the Ca(2+)-ionophore A23187, agonists that interact with different primary cell targets. ROS formation was assessed by both chemiluminescence- and fluorescence-based methods. The ROS evoked by EGF and bradykinin decayed within 8 and 4 min, respectively, this transient effect resulting probably from down-regulation of the specific agonist receptors or dissipation of the secondary signals. In contrast, the response to thapsigargin and A23187 was sustained for at least 15 min. Extracellular Ca2+ and a rise in intracellular Ca2+ concentration ([Ca2+]i) proved essential for ROS production. Chelation by BAPTA suppressed ROS formation. Direct measurement of [Ca2+]i using fura fluorescence revealed that EGF and bradykinin evoked a modest, transient [Ca2+]i elevation of less than twofold, whereas with thapsigargin and A23187 there was a sustained two- to fourfold elevation. For each agonist, the kinetics of the rise and decay of [Ca2+]i were similar to those of ROS. The enzyme(s) involved in ROS formation were inhibited by diphenyleneiodonium, indicating dependence on FAD. Our results suggest a close link between ROS and changes in [Ca2+]i generated by growth factors and hormones. This is a particularly interesting connection because elevation of ROS and/ or [Ca2+]i has been linked to cell proliferation, differentiation, and apoptosis.
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PMID:Generation of reactive oxygen species in a human keratinocyte cell line: role of calcium. 946 14