Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts

BARBARA E. SLACK; ROGER M. NITSCH; ETTA LIVNEH; GEORGE M. KUNZ; HAGIT ELDAR; RICHARD J. WURTMAN

doi:10.1111/j.1749-6632.1993.tb23040.x

Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts

BARBARA E. SLACK, ROGER M. NITSCH, ETTA LIVNEH, GEORGE M. KUNZ, HAGIT ELDAR, RICHARD J. WURTMAN

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19 Scopus citations

Abstract

Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration‐dependent manner by phorbol 12‐myristate 13‐acetate. In fibroblasts overexpressing protein kinase Co (PKCα), the EC₅₀ for this response was 7 nM, while in control cells the EC₅₀ was 63 nM. The effect of PMA was inhibited by the PKC antagonist H‐7 in control cells, but not in cells that overexpressed PKCα. Basal release of APP was higher in cells that overexpressed PKCα, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKCα regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.

Original language	English
Pages (from-to)	128-131
Number of pages	4
Journal	Annals of the New York Academy of Sciences
Volume	695
Issue number	1
DOIs	https://doi.org/10.1111/j.1749-6632.1993.tb23040.x
State	Published - 1 Jan 1993
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
History and Philosophy of Science

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10.1111/j.1749-6632.1993.tb23040.x

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title = "Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts",

abstract = "Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration‐dependent manner by phorbol 12‐myristate 13‐acetate. In fibroblasts overexpressing protein kinase Co (PKCα), the EC50 for this response was 7 nM, while in control cells the EC50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H‐7 in control cells, but not in cells that overexpressed PKCα. Basal release of APP was higher in cells that overexpressed PKCα, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKCα regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.",

author = "SLACK, \{BARBARA E.\} and NITSCH, \{ROGER M.\} and ETTA LIVNEH and KUNZ, \{GEORGE M.\} and HAGIT ELDAR and WURTMAN, \{RICHARD J.\}",

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T1 - Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts

AU - SLACK, BARBARA E.

AU - NITSCH, ROGER M.

AU - LIVNEH, ETTA

AU - KUNZ, GEORGE M.

AU - ELDAR, HAGIT

AU - WURTMAN, RICHARD J.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration‐dependent manner by phorbol 12‐myristate 13‐acetate. In fibroblasts overexpressing protein kinase Co (PKCα), the EC50 for this response was 7 nM, while in control cells the EC50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H‐7 in control cells, but not in cells that overexpressed PKCα. Basal release of APP was higher in cells that overexpressed PKCα, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKCα regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.

AB - Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration‐dependent manner by phorbol 12‐myristate 13‐acetate. In fibroblasts overexpressing protein kinase Co (PKCα), the EC50 for this response was 7 nM, while in control cells the EC50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H‐7 in control cells, but not in cells that overexpressed PKCα. Basal release of APP was higher in cells that overexpressed PKCα, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKCα regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.

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U2 - 10.1111/j.1749-6632.1993.tb23040.x

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JF - Annals of the New York Academy of Sciences

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Regulation of Amyloid Precursor Protein Release By Protein Kinase C in Swiss 3T3 Fibroblasts

Abstract

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