Synergetic activation of p38 mitogen-activated protein kinase and caspase-3-like proteases for execution of calyculin A-induced apoptosis but not N-methyl-D-aspartate-induced necrosis in mouse cortical neurons

Hyuk Wan Ko, Kong Sook Han, Eun Young Kim, Bo Rum Ryu, Won Joo Yoon, Yong Keun Jung, Seong Up Kim, Byoung Joo Gwag

Research output: Contribution to journalArticle

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Abstract

We examined the possibility that p38 mitogen-activated protein kinase and caspase-3 would be activated for execution of apoptosis and excitotoxicity, the two major types of neuronal death underlying hypoxic- ischemic and neurodegenerative diseases. Mouse cortical cell cultures underwent widespread neuronal apoptosis 24 h following exposure to 10-30 nM calyculin A, a selective inhibitor of Ser/Thr phosphatase I and IIA. Activity of p38 was increased 2-4 h following exposure to 30 nM calyculin A. Addition of 3-10 μM PD169316, a selective p38 inhibitor, partially attenuated calyculin A neurotoxicity. Activity of caspase-3-like proteases was increased in cortical cell cultures exposed to 30 nM calyculin A for 8-16 h as shown by cleavage of DEVD-p-nitroanilide and phosphorylated tau. Proteolysis of tau was completely blocked by addition of 100 μM N-benzyloxycarbonyl-Val-Ala- Asp-fluoromethyl ketone (z-VAD-fmk), a broad-spectrum inhibitor of caspases, but incompletely by 10 μM PD169316. Calyculin A neurotoxicity was partially sensitive to 100 μM z-VAD-fmk. Cotreatment with 10 μM PD169316 and 100 μM z-VAD-fmk showed additive neuroprotection against calyculin A. Neither PD169316 nor z-VAD-fmk showed a beneficial effect against excitotoxic neuronal necrosis induced by exposure to 20 μM NMDA. Thus, caspase-3-like proteases and p38 likely contribute to calyculin A-induced neuronal apoptosis but not NMDA-induced neuronal necrosis.

Original languageEnglish
Pages (from-to)2455-2461
Number of pages7
JournalJournal of Neurochemistry
Volume74
Issue number6
DOIs
Publication statusPublished - 2000 Jun 5

Fingerprint

Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
N-Methylaspartate
Caspase 3
Neurons
Peptide Hydrolases
Necrosis
Chemical activation
Apoptosis
Cell culture
Caspase 10
Cell Culture Techniques
Neurodegenerative diseases
Proteolysis
calyculin A
Ketones
Phosphoric Monoester Hydrolases
Neurodegenerative Diseases
PD 169316

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Ko, Hyuk Wan ; Han, Kong Sook ; Kim, Eun Young ; Ryu, Bo Rum ; Yoon, Won Joo ; Jung, Yong Keun ; Kim, Seong Up ; Gwag, Byoung Joo. / Synergetic activation of p38 mitogen-activated protein kinase and caspase-3-like proteases for execution of calyculin A-induced apoptosis but not N-methyl-D-aspartate-induced necrosis in mouse cortical neurons. In: Journal of Neurochemistry. 2000 ; Vol. 74, No. 6. pp. 2455-2461.
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abstract = "We examined the possibility that p38 mitogen-activated protein kinase and caspase-3 would be activated for execution of apoptosis and excitotoxicity, the two major types of neuronal death underlying hypoxic- ischemic and neurodegenerative diseases. Mouse cortical cell cultures underwent widespread neuronal apoptosis 24 h following exposure to 10-30 nM calyculin A, a selective inhibitor of Ser/Thr phosphatase I and IIA. Activity of p38 was increased 2-4 h following exposure to 30 nM calyculin A. Addition of 3-10 μM PD169316, a selective p38 inhibitor, partially attenuated calyculin A neurotoxicity. Activity of caspase-3-like proteases was increased in cortical cell cultures exposed to 30 nM calyculin A for 8-16 h as shown by cleavage of DEVD-p-nitroanilide and phosphorylated tau. Proteolysis of tau was completely blocked by addition of 100 μM N-benzyloxycarbonyl-Val-Ala- Asp-fluoromethyl ketone (z-VAD-fmk), a broad-spectrum inhibitor of caspases, but incompletely by 10 μM PD169316. Calyculin A neurotoxicity was partially sensitive to 100 μM z-VAD-fmk. Cotreatment with 10 μM PD169316 and 100 μM z-VAD-fmk showed additive neuroprotection against calyculin A. Neither PD169316 nor z-VAD-fmk showed a beneficial effect against excitotoxic neuronal necrosis induced by exposure to 20 μM NMDA. Thus, caspase-3-like proteases and p38 likely contribute to calyculin A-induced neuronal apoptosis but not NMDA-induced neuronal necrosis.",
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Synergetic activation of p38 mitogen-activated protein kinase and caspase-3-like proteases for execution of calyculin A-induced apoptosis but not N-methyl-D-aspartate-induced necrosis in mouse cortical neurons. / Ko, Hyuk Wan; Han, Kong Sook; Kim, Eun Young; Ryu, Bo Rum; Yoon, Won Joo; Jung, Yong Keun; Kim, Seong Up; Gwag, Byoung Joo.

In: Journal of Neurochemistry, Vol. 74, No. 6, 05.06.2000, p. 2455-2461.

Research output: Contribution to journalArticle

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T1 - Synergetic activation of p38 mitogen-activated protein kinase and caspase-3-like proteases for execution of calyculin A-induced apoptosis but not N-methyl-D-aspartate-induced necrosis in mouse cortical neurons

AU - Ko, Hyuk Wan

AU - Han, Kong Sook

AU - Kim, Eun Young

AU - Ryu, Bo Rum

AU - Yoon, Won Joo

AU - Jung, Yong Keun

AU - Kim, Seong Up

AU - Gwag, Byoung Joo

PY - 2000/6/5

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N2 - We examined the possibility that p38 mitogen-activated protein kinase and caspase-3 would be activated for execution of apoptosis and excitotoxicity, the two major types of neuronal death underlying hypoxic- ischemic and neurodegenerative diseases. Mouse cortical cell cultures underwent widespread neuronal apoptosis 24 h following exposure to 10-30 nM calyculin A, a selective inhibitor of Ser/Thr phosphatase I and IIA. Activity of p38 was increased 2-4 h following exposure to 30 nM calyculin A. Addition of 3-10 μM PD169316, a selective p38 inhibitor, partially attenuated calyculin A neurotoxicity. Activity of caspase-3-like proteases was increased in cortical cell cultures exposed to 30 nM calyculin A for 8-16 h as shown by cleavage of DEVD-p-nitroanilide and phosphorylated tau. Proteolysis of tau was completely blocked by addition of 100 μM N-benzyloxycarbonyl-Val-Ala- Asp-fluoromethyl ketone (z-VAD-fmk), a broad-spectrum inhibitor of caspases, but incompletely by 10 μM PD169316. Calyculin A neurotoxicity was partially sensitive to 100 μM z-VAD-fmk. Cotreatment with 10 μM PD169316 and 100 μM z-VAD-fmk showed additive neuroprotection against calyculin A. Neither PD169316 nor z-VAD-fmk showed a beneficial effect against excitotoxic neuronal necrosis induced by exposure to 20 μM NMDA. Thus, caspase-3-like proteases and p38 likely contribute to calyculin A-induced neuronal apoptosis but not NMDA-induced neuronal necrosis.

AB - We examined the possibility that p38 mitogen-activated protein kinase and caspase-3 would be activated for execution of apoptosis and excitotoxicity, the two major types of neuronal death underlying hypoxic- ischemic and neurodegenerative diseases. Mouse cortical cell cultures underwent widespread neuronal apoptosis 24 h following exposure to 10-30 nM calyculin A, a selective inhibitor of Ser/Thr phosphatase I and IIA. Activity of p38 was increased 2-4 h following exposure to 30 nM calyculin A. Addition of 3-10 μM PD169316, a selective p38 inhibitor, partially attenuated calyculin A neurotoxicity. Activity of caspase-3-like proteases was increased in cortical cell cultures exposed to 30 nM calyculin A for 8-16 h as shown by cleavage of DEVD-p-nitroanilide and phosphorylated tau. Proteolysis of tau was completely blocked by addition of 100 μM N-benzyloxycarbonyl-Val-Ala- Asp-fluoromethyl ketone (z-VAD-fmk), a broad-spectrum inhibitor of caspases, but incompletely by 10 μM PD169316. Calyculin A neurotoxicity was partially sensitive to 100 μM z-VAD-fmk. Cotreatment with 10 μM PD169316 and 100 μM z-VAD-fmk showed additive neuroprotection against calyculin A. Neither PD169316 nor z-VAD-fmk showed a beneficial effect against excitotoxic neuronal necrosis induced by exposure to 20 μM NMDA. Thus, caspase-3-like proteases and p38 likely contribute to calyculin A-induced neuronal apoptosis but not NMDA-induced neuronal necrosis.

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