Abstract
We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lines. Necrosis in CEM cells, characterized by cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-mediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na+/Ca2+ exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 μM A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lines might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium.
| Original language | English |
|---|---|
| Pages (from-to) | 187-196 |
| Number of pages | 10 |
| Journal | European Journal of Pharmacology |
| Volume | 516 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jun 15 2005 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Bcl-2
- Calcium ionophore
- Clonazepam
- Mitochondria
- Necrosis
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by A23187 in CEM cells. / Hamahata, Keigo; Adachi, Souichi; Matsubara, Hiroshi; Okada, Masayuki; Imai, Tsuyoshi; Watanabe, Ken Ichiro; Toyokuni, Shin Ya; Ueno, Masaki; Wakabayashi, Shigeo; Katanosaka, Yuki; Akiba, Satoshi; Kubota, Masaru; Nakahata, Tatsutoshi.
In: European Journal of Pharmacology, Vol. 516, No. 3, 15.06.2005, p. 187-196.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by A23187 in CEM cells
AU - Hamahata, Keigo
AU - Adachi, Souichi
AU - Matsubara, Hiroshi
AU - Okada, Masayuki
AU - Imai, Tsuyoshi
AU - Watanabe, Ken Ichiro
AU - Toyokuni, Shin Ya
AU - Ueno, Masaki
AU - Wakabayashi, Shigeo
AU - Katanosaka, Yuki
AU - Akiba, Satoshi
AU - Kubota, Masaru
AU - Nakahata, Tatsutoshi
PY - 2005/6/15
Y1 - 2005/6/15
N2 - We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lines. Necrosis in CEM cells, characterized by cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-mediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na+/Ca2+ exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 μM A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lines might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium.
AB - We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lines. Necrosis in CEM cells, characterized by cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-mediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na+/Ca2+ exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 μM A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lines might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium.
KW - Apoptosis
KW - Bcl-2
KW - Calcium ionophore
KW - Clonazepam
KW - Mitochondria
KW - Necrosis
UR - http://www.scopus.com/inward/record.url?scp=21544437612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21544437612&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.04.018
DO - 10.1016/j.ejphar.2005.04.018
M3 - Article
C2 - 15963976
AN - SCOPUS:21544437612
VL - 516
SP - 187
EP - 196
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -