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Calcium ions are released from intracellular stores in response to agonist-stimulated production of inositol 1,4,5-trisphosphate (InsP3), a second messenger generated at the cell membrane. Depletion of Ca2+ from internal stores triggers a capacitative influx of extracellular Ca2+ across the plasma membrane. The influx of Ca2+ can be recorded as(More)
Members of the bcl-2 gene family encode proteins that function either to promote or to inhibit apoptosis. Despite numerous efforts, the mechanism of action of Bcl-2, an anti-apoptotic protein, is still not clear. In particular, the relation between Bcl-2 and the endoplasmic reticulum (ER) calcium store is not well-understood. In the present work, we(More)
In polarized epithelial cells [Ca2+]i waves are initiated in discrete regions and propagate through the cytosol. The structural basis for these compartmentalized and coordinated events are not well understood. In the present study we used a combination of [Ca2+]i imaging at high temporal resolution, recording of Ca2+-activated Cl- current, and(More)
We have investigated the role of mitochondrial Ca(2+) (Ca(m)) homeostasis in cell survival. Disruption of Ca(m) homeostasis via depletion of the mitochondrial Ca(2+) store was the earliest event that occurred during staurosporine-induced apoptosis in neuroblastoma cells (SH-SY5Y). The decrease of Ca(m) preceded activation of the caspase cascade and DNA(More)
The present study was aimed at localization of plasma membrane (PMCA) and intracellular (SERCA) Ca2+ pumps and characterizing their role in initiation and propagation of Ca2+ waves. Specific and polarized expression of Ca2+ pumps was observed in all epithelial cells examined. Immunolocalization revealed expression of PMCA in both the basolateral and luminal(More)
Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, > 100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed'' only favorable "soil'' offered by certain groups. The hypothesis implies that cancer cells must find a suitable "soil'' in a target organ--i.e., one(More)
Using distinct models of apoptosis and necrosis, we have investigated the effect of mitochondrial Ca(2+)(Ca(m)) homeostasis in the regulation of cell death in neuroblastoma cells as well as cardiac myocytes. The steady state level of Ca(m)was determined as the FCCP-releasable Ca(2+). Culturing cells with low concentration of extracellular Ca(2+)(Ca(o)) or(More)
Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects the mitochondrial Na(+)-Ca(2+) exchange(More)
We have developed a novel in vivo model of human small-cell lung carcinoma (SCLC) using orthotopic reconstitution by injecting human SCLC in the tail vein of severe combined immunodeficient (SCID) mice whereby the SCLC grows in the lung and other organs. Cisplatin (DDP) had significant antitumor effects on the SCLC growing orthotopically in the lung whereas(More)
Long chain saturated beta-hydroxy fatty acid content and oxidative metabolism were studied in hearts of diabetic mice (C57BL/KsJ db/db) with a progressive cardiomyopathy at intervals of 7, 10, 16, and 26 wk of age. Total beta-hydroxy fatty acid (BHFA) content increases progressively with age in diabetic hearts with a mean value of 143.5 nmol/g dry wt as(More)