| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201
The mechanism by which Bcl-2 inhibits cell death is unknown. It has been suggested that Bcl-2 functions as an antioxidant. Because Bcl-2 is localized mainly to the membranes of the endoplasmic reticulum (ER) and the mitochondria, which represent the main intracellular storage sites for Ca2+, we hypothesized that Bcl-2 might protect cells against oxidant injury by altering intracellular Ca2+ homeostasis. To test this hypothesis, we examined the effect of oxidant treatment on viability in normal rat kidney (NRK) cells and in NRK cells stably transfected with Bcl-2 in the presence or absence of intracellular Ca2+, and we compared the effect of Bcl-2 expression on oxidant-induced intracellular Ca2+ mobilization and on ER and mitochondrial Ca2+ pools. NRK cells transfected with Bcl-2 (NRK-Bcl-2) were significantly more resistant to H2O2-induced cytotoxicity than control cells. EGTA-AM, an intracellular Ca2+ chelator, as well as the absence of Ca2+ in the medium, reduced H2O2-induced cytotoxicity in both cell lines. Compared with controls, cells overexpressing Bcl-2 showed a delayed rise in intracellular Ca2+ concentration ([Ca2+]i) after H2O2 treatment. After treatment with the Ca2+ ionophore ionomycin, Bcl-2-transfected cells showed a much quicker decrease after the maximal rise than control cells, suggesting stronger intracellular Ca2+ buffering, whereas treatment with thapsigargin, an inhibitor of the ER Ca2+-ATPases, transiently increased [Ca2+]i in control and in Bcl-2-transfected cells. Estimates of mitochondrial Ca2+ stores using an uncoupler of oxidative phosphorylation show that NRK-Bcl-2 cells have a higher capacity for mitochondrial Ca2+ storage than control cells. In conclusion, Bcl-2 may prevent oxidant-induced cell death, in part, by increasing the capacity of mitochondria to store Ca2+.
mitochondrial membrane potential; calcium ionophore; oxidative stress
This article has been cited by other articles:
|
|
 |
|
  F. Selimi, M. W. Vogel, and J. Mariani Bax Inactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons J. Neurosci., July 15, 2000; 20(14): 5339 - 5345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Azzouz, A. Hottinger, J.-C. Paterna, A. D. Zurn, P. Aebischer, and H. Bueler Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2 Hum. Mol. Genet., March 22, 2000; 9(5): 803 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Chang, P. C. Phelps, I. K. Berezesky, M. L. Ebersberger Jr., and B. F. Trump Studies on the Mechanisms and Kinetics of Apoptosis Induced by Microinjection of Cytochrome c in Rat Kidney Tubule Epithelial Cells (NRK-52E) Am. J. Pathol., February 1, 2000; 156(2): 637 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Pan, M. B. Bhat, A.-L. Nieminen, and J. Ma Synergistic Movements of Ca2+ and Bax in Cells Undergoing Apoptosis J. Biol. Chem., August 17, 2001; 276(34): 32257 - 32263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Pan, D. Damron, A.-L. Nieminen, M. B. Bhat, and J. Ma Depletion of Intracellular Ca2+ by Caffeine and Ryanodine Induces Apoptosis of Chinese Hamster Ovary Cells Transfected with Ryanodine Receptor J. Biol. Chem., June 23, 2000; 275(26): 19978 - 19984. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
