Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures

K Sennvik, Eirikur Benedikz, J Fastbom, E Sundström, B Winblad, M Ankarcrona

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Alzheimer's disease (AD) is characterized by the degeneration and loss of neurons, intracellular neurofibrillary tangles and the accumulation of extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta is generated from the amyloid precursor protein (APP) by sequential beta- and gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta region by alpha-secretase, preventing A beta formation. Here we investigated APP processing and secretion in primary neurons, using either colchicine or the calcium ionophore A23187 to induce apoptosis. Cell viability was determined by MTT measurements and apoptosis was further confirmed by annexin V and propidium iodide staining. We found that exposure to A23187 significantly decreased the secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase-dependent manner, although the secretion of total soluble APP beta sAPP) did not change. In addition, caspase inhibition restored cell viability to control levels. Exposure to colchicine did not change the amount of either secreted beta-sAPP or total sAPP and caspase inhibition was only partially able to restore cell viability. We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP.
OriginalsprogEngelsk
TidsskriftJournal of Neuroscience Research
Vol/bind63
Udgave nummer5
Sider (fra-til)429-37
Antal sider9
ISSN0360-4012
StatusUdgivet - 2001

Fingeraftryk

Calcium Ionophores
Calcimycin
Apoptosis
Cell Survival
Colchicine
Neurofibrillary Tangles
Propidium
Annexin A5
Amyloid beta-Peptides
Amyloid Plaques
Alzheimer Disease
Homeostasis
Neurons

Citer dette

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title = "Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures",
abstract = "Alzheimer's disease (AD) is characterized by the degeneration and loss of neurons, intracellular neurofibrillary tangles and the accumulation of extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta is generated from the amyloid precursor protein (APP) by sequential beta- and gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta region by alpha-secretase, preventing A beta formation. Here we investigated APP processing and secretion in primary neurons, using either colchicine or the calcium ionophore A23187 to induce apoptosis. Cell viability was determined by MTT measurements and apoptosis was further confirmed by annexin V and propidium iodide staining. We found that exposure to A23187 significantly decreased the secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase-dependent manner, although the secretion of total soluble APP beta sAPP) did not change. In addition, caspase inhibition restored cell viability to control levels. Exposure to colchicine did not change the amount of either secreted beta-sAPP or total sAPP and caspase inhibition was only partially able to restore cell viability. We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP.",
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author = "K Sennvik and Eirikur Benedikz and J Fastbom and E Sundstr{\"o}m and B Winblad and M Ankarcrona",
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language = "English",
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Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures. / Sennvik, K; Benedikz, Eirikur; Fastbom, J; Sundström, E; Winblad, B; Ankarcrona, M.

I: Journal of Neuroscience Research, Bind 63, Nr. 5, 2001, s. 429-37.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures

AU - Sennvik, K

AU - Benedikz, Eirikur

AU - Fastbom, J

AU - Sundström, E

AU - Winblad, B

AU - Ankarcrona, M

N1 - Copyright 2001 Wiley-Liss, Inc.

PY - 2001

Y1 - 2001

N2 - Alzheimer's disease (AD) is characterized by the degeneration and loss of neurons, intracellular neurofibrillary tangles and the accumulation of extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta is generated from the amyloid precursor protein (APP) by sequential beta- and gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta region by alpha-secretase, preventing A beta formation. Here we investigated APP processing and secretion in primary neurons, using either colchicine or the calcium ionophore A23187 to induce apoptosis. Cell viability was determined by MTT measurements and apoptosis was further confirmed by annexin V and propidium iodide staining. We found that exposure to A23187 significantly decreased the secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase-dependent manner, although the secretion of total soluble APP beta sAPP) did not change. In addition, caspase inhibition restored cell viability to control levels. Exposure to colchicine did not change the amount of either secreted beta-sAPP or total sAPP and caspase inhibition was only partially able to restore cell viability. We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP.

AB - Alzheimer's disease (AD) is characterized by the degeneration and loss of neurons, intracellular neurofibrillary tangles and the accumulation of extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta is generated from the amyloid precursor protein (APP) by sequential beta- and gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta region by alpha-secretase, preventing A beta formation. Here we investigated APP processing and secretion in primary neurons, using either colchicine or the calcium ionophore A23187 to induce apoptosis. Cell viability was determined by MTT measurements and apoptosis was further confirmed by annexin V and propidium iodide staining. We found that exposure to A23187 significantly decreased the secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase-dependent manner, although the secretion of total soluble APP beta sAPP) did not change. In addition, caspase inhibition restored cell viability to control levels. Exposure to colchicine did not change the amount of either secreted beta-sAPP or total sAPP and caspase inhibition was only partially able to restore cell viability. We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP.

KW - Amino Acid Chloromethyl Ketones

KW - Amyloid Precursor Protein Secretases

KW - Amyloid beta-Protein Precursor

KW - Animals

KW - Annexin A5

KW - Apoptosis

KW - Aspartic Acid Endopeptidases

KW - Biological Transport

KW - Blotting, Western

KW - Calcimycin

KW - Calcium

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Colchicine

KW - Culture Media, Conditioned

KW - Cysteine Proteinase Inhibitors

KW - Cytoskeleton

KW - Endopeptidases

KW - Ionophores

KW - Neurons

KW - Rats

KW - Rats, Sprague-Dawley

M3 - Journal article

VL - 63

SP - 429

EP - 437

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -