TGFβ1 enhances formation of cellular Aβ/apoE deposits in vascular myocytes

Bozena Mazur-Kolecka; Janusz Frackowiak; Harrye Le Vine; Taraneh Haske; Lori Evans; Thirasak Sukontasup; Adam Golabek

doi:10.1016/S0197-4580(02)00095-7

TGFβ1 enhances formation of cellular Aβ/apoE deposits in vascular myocytes

Bozena Mazur-Kolecka, Janusz Frackowiak, Harrye Le Vine, Taraneh Haske, Lori Evans, Thirasak Sukontasup, Adam Golabek

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-β protein (Aβ) in cells exposed to transforming growth factor β1 (TGFβ1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in β-amyloidosis in vivo and produce Aβ in cell culture. We found that cell treatment with TGFβ1 together with apoE4 strongly increased the amount of cellular Aβ. The intracellular Aβ co-localized with apoE but not with TGFβ, similarly as in vascular β-amyloid. Some cellular Aβ/apoE deposits increased in size and persisted in culture even after the TGFβ1 and apoE4 were removed. The appearance of cellular deposits of Aβ was associated with increased production of the amyloid-β precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFβ1 can trigger vascular β-amyloidosis by inducing intracellular formation of stable Aβ/apoE deposits.

Original language	English
Pages (from-to)	355-364
Number of pages	10
Journal	Neurobiology of Aging
Volume	24
Issue number	2
DOIs	https://doi.org/10.1016/S0197-4580(02)00095-7
State	Published - Mar 2003

Bibliographical note

Funding Information:
The research was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institute of Aging, NIH, No. PO1 AG 04220. The authors want to thank Anna Potempska, PhD (IBR, Staten Island, NY), for affinity-purified antiserum R162; Pankaj Mehta, PhD (IBR), for antiserum R57; Kwang Soo Kim, PhD (IBR) for mAbs 4G8 and 6E10; and George Merz, PhD (IBR), for assistance with confocal microscopy studies.

Funding

The research was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institute of Aging, NIH, No. PO1 AG 04220. The authors want to thank Anna Potempska, PhD (IBR, Staten Island, NY), for affinity-purified antiserum R162; Pankaj Mehta, PhD (IBR), for antiserum R57; Kwang Soo Kim, PhD (IBR) for mAbs 4G8 and 6E10; and George Merz, PhD (IBR), for assistance with confocal microscopy studies.

Funders	Funder number
National Institutes of Health (NIH)
National Institute on Aging	P01AG004220
New York State Developmental Disabilities Planning Council

Keywords

ApoE4
Cell culture
Smooth muscle cells
TGFβ1
Vascular amyloidosis
β-Amyloidogenesis

ASJC Scopus subject areas

General Neuroscience
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/S0197-4580(02)00095-7

Cite this

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title = "TGFβ1 enhances formation of cellular Aβ/apoE deposits in vascular myocytes",

abstract = "Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-β protein (Aβ) in cells exposed to transforming growth factor β1 (TGFβ1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in β-amyloidosis in vivo and produce Aβ in cell culture. We found that cell treatment with TGFβ1 together with apoE4 strongly increased the amount of cellular Aβ. The intracellular Aβ co-localized with apoE but not with TGFβ, similarly as in vascular β-amyloid. Some cellular Aβ/apoE deposits increased in size and persisted in culture even after the TGFβ1 and apoE4 were removed. The appearance of cellular deposits of Aβ was associated with increased production of the amyloid-β precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFβ1 can trigger vascular β-amyloidosis by inducing intracellular formation of stable Aβ/apoE deposits.",

keywords = "ApoE4, Cell culture, Smooth muscle cells, TGFβ1, Vascular amyloidosis, β-Amyloidogenesis",

author = "Bozena Mazur-Kolecka and Janusz Frackowiak and {Le Vine}, Harrye and Taraneh Haske and Lori Evans and Thirasak Sukontasup and Adam Golabek",

note = "Funding Information: The research was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institute of Aging, NIH, No. PO1 AG 04220. The authors want to thank Anna Potempska, PhD (IBR, Staten Island, NY), for affinity-purified antiserum R162; Pankaj Mehta, PhD (IBR), for antiserum R57; Kwang Soo Kim, PhD (IBR) for mAbs 4G8 and 6E10; and George Merz, PhD (IBR), for assistance with confocal microscopy studies. ",

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AU - Frackowiak, Janusz

AU - Le Vine, Harrye

AU - Haske, Taraneh

AU - Evans, Lori

AU - Sukontasup, Thirasak

AU - Golabek, Adam

N1 - Funding Information: The research was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institute of Aging, NIH, No. PO1 AG 04220. The authors want to thank Anna Potempska, PhD (IBR, Staten Island, NY), for affinity-purified antiserum R162; Pankaj Mehta, PhD (IBR), for antiserum R57; Kwang Soo Kim, PhD (IBR) for mAbs 4G8 and 6E10; and George Merz, PhD (IBR), for assistance with confocal microscopy studies.

PY - 2003/3

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N2 - Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-β protein (Aβ) in cells exposed to transforming growth factor β1 (TGFβ1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in β-amyloidosis in vivo and produce Aβ in cell culture. We found that cell treatment with TGFβ1 together with apoE4 strongly increased the amount of cellular Aβ. The intracellular Aβ co-localized with apoE but not with TGFβ, similarly as in vascular β-amyloid. Some cellular Aβ/apoE deposits increased in size and persisted in culture even after the TGFβ1 and apoE4 were removed. The appearance of cellular deposits of Aβ was associated with increased production of the amyloid-β precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFβ1 can trigger vascular β-amyloidosis by inducing intracellular formation of stable Aβ/apoE deposits.

AB - Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-β protein (Aβ) in cells exposed to transforming growth factor β1 (TGFβ1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in β-amyloidosis in vivo and produce Aβ in cell culture. We found that cell treatment with TGFβ1 together with apoE4 strongly increased the amount of cellular Aβ. The intracellular Aβ co-localized with apoE but not with TGFβ, similarly as in vascular β-amyloid. Some cellular Aβ/apoE deposits increased in size and persisted in culture even after the TGFβ1 and apoE4 were removed. The appearance of cellular deposits of Aβ was associated with increased production of the amyloid-β precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFβ1 can trigger vascular β-amyloidosis by inducing intracellular formation of stable Aβ/apoE deposits.

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KW - Cell culture

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KW - Vascular amyloidosis

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TGFβ1 enhances formation of cellular Aβ/apoE deposits in vascular myocytes

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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