Bcl-x(L) blocks a mitochondrial inner membrane channel and prevents Ca2+ overload-mediated cell death
(2011) In PLoS ONE 6(6). p.20423-20423- Abstract
Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca(2+) is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial... (More)
Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca(2+) is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial mechanisms involved in the neuroprotective effect of Bcl-x(L) on Ca(2+) overload-mediated cell death in human neuroblastoma SH-SY5Y cells. We have found that Bcl-x(L) neuroprotective actions take place at mitochondria where this antiapoptotic protein delays both mitochondrial potential collapse and opening of the permeability transition pore by preventing Ca(2+)-mediated mitochondrial multiple conductance channel opening. Bcl-x(L) neuroprotective actions were antagonized by the Bcl-x(L) inhibitor ABT-737 and potentiated by the Ca(2+) chelator BAPTA-AM. As a consequence, this would prevent free radical production, mitochondrial membrane permeabilization, release from mitochondria of pro-apoptotic molecules, caspase activation and cellular death.
(Less)
- author
- Tornero, Daniel LU ; Posadas, Inmaculada and Ceña, Valentín
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- keywords
- Apoptosis, Biological Transport, Biphenyl Compounds, Calcium, Caspases, Cell Line, Tumor, Egtazic Acid, Gene Expression Regulation, Humans, Ion Channel Gating, Ion Channels, Ionomycin, Membrane Potential, Mitochondrial, Mitochondria, Mitochondrial Membranes, Nitrophenols, Patch-Clamp Techniques, Permeability, Piperazines, Single-Cell Analysis, Sulfonamides, bcl-X Protein
- in
- PLoS ONE
- volume
- 6
- issue
- 6
- pages
- 20423 - 20423
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:21674052
- scopus:79957936182
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0020423
- language
- English
- LU publication?
- no
- id
- 815cf627-0598-4750-8055-67f2c5ac89a3
- date added to LUP
- 2016-04-11 15:19:56
- date last changed
- 2024-05-02 22:46:11
@article{815cf627-0598-4750-8055-67f2c5ac89a3,
abstract = {{<p>Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca(2+) is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial mechanisms involved in the neuroprotective effect of Bcl-x(L) on Ca(2+) overload-mediated cell death in human neuroblastoma SH-SY5Y cells. We have found that Bcl-x(L) neuroprotective actions take place at mitochondria where this antiapoptotic protein delays both mitochondrial potential collapse and opening of the permeability transition pore by preventing Ca(2+)-mediated mitochondrial multiple conductance channel opening. Bcl-x(L) neuroprotective actions were antagonized by the Bcl-x(L) inhibitor ABT-737 and potentiated by the Ca(2+) chelator BAPTA-AM. As a consequence, this would prevent free radical production, mitochondrial membrane permeabilization, release from mitochondria of pro-apoptotic molecules, caspase activation and cellular death.</p>}},
author = {{Tornero, Daniel and Posadas, Inmaculada and Ceña, Valentín}},
issn = {{1932-6203}},
keywords = {{Apoptosis; Biological Transport; Biphenyl Compounds; Calcium; Caspases; Cell Line, Tumor; Egtazic Acid; Gene Expression Regulation; Humans; Ion Channel Gating; Ion Channels; Ionomycin; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Membranes; Nitrophenols; Patch-Clamp Techniques; Permeability; Piperazines; Single-Cell Analysis; Sulfonamides; bcl-X Protein}},
language = {{eng}},
number = {{6}},
pages = {{20423--20423}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Bcl-x(L) blocks a mitochondrial inner membrane channel and prevents Ca2+ overload-mediated cell death}},
url = {{http://dx.doi.org/10.1371/journal.pone.0020423}},
doi = {{10.1371/journal.pone.0020423}},
volume = {{6}},
year = {{2011}},
}