DOI: 10.1002/jnr.1064. Elevated vulnerability to oxidative stress‐induced cell death and activation of caspase‐3 by the Swedish amyloid precursor protein mutation

Elevated vulnerability to oxidative stress‐induced cell death and activation of caspase‐3 by the Swedish amyloid precursor protein mutation

10.1002/jnr.1064

Crossref journal-article

Wiley

Journal of Neuroscience Research (311)

Abstract

AbstractThe Swedish double mutation (KM670/671NL) of amyloid precursor protein (APPsw) is associated with early‐onset familial Alzheimer's disease (FAD) and results in from three‐ to sixfold increased β‐amyloid production. The goal of the present study was to elucidate the effects of APPsw on mechanisms of apoptotic cell death. Therefore, PC12 cells were stably transfected with human APPsw. Here we report that the vulnerability of APPsw‐bearing PC12 cells to undergo apoptotic cell death was significantly enhanced after exposure to hydrogen peroxide compared to human wild‐type APP‐bearing cells, empty vector‐transfected cells, and parent untransfected cells. In addition, we have analyzed the potential influence of several mechanisms that can interfere with the execution of the apoptotic cell death program: the inhibition of cell death by the use of caspase inhibitors and the reduction of oxidative stress by the use of (±)‐α‐tocopherol (vitamin E). Interestingly, oxidative stress‐induced cell death was significantly attenuated in APPsw PC12 cells by pretreatment with caspase‐3 inhibitors but not with caspase‐1 inhibitors. In parallel, caspase‐3 activity was markedly elevated in APPsw PC12 after stimulation with hydrogen peroxide for 6 hr, whereas caspase‐1 activity was unaltered. In addition, oxidative stress‐induced cell death could be reduced after pretreatment of APPsw cells with (±)‐α‐tocopherol. The protective potency of (±)‐α‐tocopherol was even greater than that of caspase‐3 inhibitors. Our findings further emphasize the role of mutations in the amyloid precursor protein in apoptotic cell death and may provide the fundamental basis for further efforts to elucidate the underlying processes caused by FAD‐related mutations. J. Neurosci. Res. 64:183–192, 2001. © 2001 Wiley‐Liss, Inc.

Bibliography

Eckert, A., Steiner, B., Marques, C., Leutz, S., Romig, H., Haass, C., & MÃ¼ller, W. E. (2001). Elevated vulnerability to oxidative stressâinduced cell death and activation of caspaseâ3 by the Swedish amyloid precursor protein mutation. Journal of Neuroscience Research, 64(2), 183â192. Portico.

Authors 7

Anne Eckert (first)
Barbara Steiner (additional)
Celio Marques (additional)
Steffen Leutz (additional)
Helmut Romig (additional)
Christian Haass (additional)
Walter E. Müller (additional)

References 51 Referenced 80

Dates

Type	When
Created	23 years ago (Aug. 25, 2002, 5:30 p.m.)
Deposited	1 year, 9 months ago (Nov. 19, 2023, 8:58 a.m.)
Indexed	4 months, 2 weeks ago (April 16, 2025, 8:05 a.m.)
Issued	24 years, 5 months ago (March 29, 2001)
Published	24 years, 5 months ago (March 29, 2001)
Published Online	24 years, 5 months ago (March 29, 2001)
Published Print	24 years, 4 months ago (April 15, 2001)

Funders 3

Deutsche Forschungsgemeinschaft 10.13039/501100001659
Region: Europe
gov (National government)
Labels3
1. German Research Association
2. German Research Foundation
3. DFG
Awards1
1. Mu467/8-1
Fonds der Chemischen Industrie
Alzheimer Forschung Initiative 10.13039/100010146
Region: Europe
pri (Other non-profit organizations)
Labels2
1. Alzheimer Forschung Initiative e.V.
2. AFI

BibTeX

@article{Eckert_2001, title={Elevated vulnerability to oxidative stress‐induced cell death and activation of caspase‐3 by the Swedish amyloid precursor protein mutation}, volume={64}, ISSN={1097-4547}, url={http://dx.doi.org/10.1002/jnr.1064}, DOI={10.1002/jnr.1064}, number={2}, journal={Journal of Neuroscience Research}, publisher={Wiley}, author={Eckert, Anne and Steiner, Barbara and Marques, Celio and Leutz, Steffen and Romig, Helmut and Haass, Christian and Müller, Walter E.}, year={2001}, month=mar, pages={183–192} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        4,
        16
      ]
    ],
    "date-time": "2025-04-16T12:05:10Z",
    "timestamp": 1744805110713,
    "version": "3.37.3"
  },
  "reference-count": 51,
  "publisher": "Wiley",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            3,
            29
          ]
        ],
        "date-time": "2001-03-29T00:00:00Z",
        "timestamp": 985824000000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "funder": [
    {
      "DOI": "10.13039/501100001659",
      "name": "Deutsche Forschungsgemeinschaft",
      "doi-asserted-by": "crossref",
      "award": [
        "Mu467/8-1"
      ],
      "id": [
        {
          "id": "10.13039/501100001659",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "name": "Fonds der Chemischen Industrie"
    },
    {
      "DOI": "10.13039/100010146",
      "name": "Alzheimer Forschung Initiative",
      "doi-asserted-by": "crossref",
      "id": [
        {
          "id": "10.13039/100010146",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        4,
        15
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>The Swedish double mutation (KM670/671NL) of amyloid precursor protein (APPsw) is associated with early\u2010onset familial Alzheimer's disease (FAD) and results in from three\u2010 to sixfold increased \u03b2\u2010amyloid production. The goal of the present study was to elucidate the effects of APPsw on mechanisms of apoptotic cell death. Therefore, PC12 cells were stably transfected with human APPsw. Here we report that the vulnerability of APPsw\u2010bearing PC12 cells to undergo apoptotic cell death was significantly enhanced after exposure to hydrogen peroxide compared to human wild\u2010type APP\u2010bearing cells, empty vector\u2010transfected cells, and parent untransfected cells. In addition, we have analyzed the potential influence of several mechanisms that can interfere with the execution of the apoptotic cell death program: the inhibition of cell death by the use of caspase inhibitors and the reduction of oxidative stress by the use of (\u00b1)\u2010\u03b1\u2010tocopherol (vitamin E). Interestingly, oxidative stress\u2010induced cell death was significantly attenuated in APPsw PC12 cells by pretreatment with caspase\u20103 inhibitors but not with caspase\u20101 inhibitors. In parallel, caspase\u20103 activity was markedly elevated in APPsw PC12 after stimulation with hydrogen peroxide for 6 hr, whereas caspase\u20101 activity was unaltered. In addition, oxidative stress\u2010induced cell death could be reduced after pretreatment of APPsw cells with (\u00b1)\u2010\u03b1\u2010tocopherol. The protective potency of (\u00b1)\u2010\u03b1\u2010tocopherol was even greater than that of caspase\u20103 inhibitors. Our findings further emphasize the role of mutations in the amyloid precursor protein in apoptotic cell death and may provide the fundamental basis for further efforts to elucidate the underlying processes caused by FAD\u2010related mutations. J. Neurosci. Res. 64:183\u2013192, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.</jats:p>",
  "DOI": "10.1002/jnr.1064",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        8,
        25
      ]
    ],
    "date-time": "2002-08-25T21:30:12Z",
    "timestamp": 1030311012000
  },
  "page": "183-192",
  "source": "Crossref",
  "is-referenced-by-count": 80,
  "title": "Elevated vulnerability to oxidative stress\u2010induced cell death and activation of caspase\u20103 by the Swedish amyloid precursor protein mutation",
  "prefix": "10.1002",
  "volume": "64",
  "author": [
    {
      "given": "Anne",
      "family": "Eckert",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Barbara",
      "family": "Steiner",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Celio",
      "family": "Marques",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Steffen",
      "family": "Leutz",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Helmut",
      "family": "Romig",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Christian",
      "family": "Haass",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Walter E.",
      "family": "M\u00fcller",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2001,
        3,
        29
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1994.1508"
    },
    {
      "key": "e_1_2_6_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/360672a0"
    },
    {
      "key": "e_1_2_6_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.25.11993"
    },
    {
      "key": "e_1_2_6_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm0197-67"
    },
    {
      "key": "e_1_2_6_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0197-4580(98)00042-6"
    },
    {
      "key": "e_1_2_6_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0306-4522(98)00162-6"
    },
    {
      "key": "e_1_2_6_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0301-0082(99)00033-7"
    },
    {
      "key": "e_1_2_6_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(96)01142-8"
    },
    {
      "key": "e_1_2_6_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1159/000051242"
    },
    {
      "key": "e_1_2_6_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/nbdi.2000.0378"
    },
    {
      "key": "e_1_2_6_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.119.3.493"
    },
    {
      "key": "e_1_2_6_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80748-5"
    },
    {
      "key": "e_1_2_6_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/349704a0"
    },
    {
      "key": "e_1_2_6_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.73.7.2424"
    },
    {
      "key": "e_1_2_6_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.17-11-04212.1997"
    },
    {
      "key": "e_1_2_6_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1999.0721019.x"
    },
    {
      "key": "e_1_2_6_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm1295-1291"
    },
    {
      "key": "e_1_2_6_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-8993(99)01808-9"
    },
    {
      "key": "e_1_2_6_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.8.3270"
    },
    {
      "key": "e_1_2_6_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0197-0186(94)90056-6"
    },
    {
      "key": "e_1_2_6_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.18-12-04439.1998"
    },
    {
      "key": "e_1_2_6_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1999.0732278.x"
    },
    {
      "key": "e_1_2_6_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0197-4580(92)90053-Z"
    },
    {
      "key": "e_1_2_6_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0195-21"
    },
    {
      "key": "e_1_2_6_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi991453n"
    },
    {
      "key": "e_1_2_6_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.17.7951"
    },
    {
      "key": "e_1_2_6_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-4547(19990301)55:5<629::AID-JNR10>3.0.CO;2-Y"
    },
    {
      "key": "e_1_2_6_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1080/10715769900300081"
    },
    {
      "key": "e_1_2_6_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.12-02-00376.1992"
    },
    {
      "key": "e_1_2_6_31_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/47377"
    },
    {
      "key": "e_1_2_6_32_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1999.0731155.x"
    },
    {
      "key": "e_1_2_6_33_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-1759(91)90198-O"
    },
    {
      "key": "e_1_2_6_34_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.18-03-00830.1998"
    },
    {
      "key": "e_1_2_6_35_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.30.21011"
    },
    {
      "key": "e_1_2_6_36_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.85.19.7341"
    },
    {
      "key": "e_1_2_6_37_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1749-6632.1996.tb34401.x"
    },
    {
      "key": "e_1_2_6_38_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0002-9440(10)65460-0"
    },
    {
      "key": "e_1_2_6_39_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.48.32322"
    },
    {
      "key": "e_1_2_6_40_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/oxfordjournals.jbchem.a022287"
    },
    {
      "key": "e_1_2_6_41_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8191290"
    },
    {
      "key": "e_1_2_6_42_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0306-4522(99)00432-7"
    },
    {
      "key": "e_1_2_6_43_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.281.5381.1312"
    },
    {
      "key": "e_1_2_6_44_1",
      "doi-asserted-by": "crossref",
      "first-page": "6955",
      "DOI": "10.1523/JNEUROSCI.19-16-06955.1999",
      "article-title": "Activation of neuronal caspase\u20103 by intracellular accumulation of wild\u2010type Alzheimer amyloid precursor protein",
      "volume": "19",
      "author": "Uetsuki T",
      "year": "1999",
      "journal-title": "J Neurosci"
    },
    {
      "key": "e_1_2_6_45_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.9.5823"
    },
    {
      "key": "e_1_2_6_46_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.20.9513"
    },
    {
      "key": "e_1_2_6_47_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.274.5293.1710"
    },
    {
      "key": "e_1_2_6_48_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.13.7547"
    },
    {
      "key": "e_1_2_6_49_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.272.5266.1349"
    },
    {
      "key": "e_1_2_6_50_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1996.tb00382.x"
    },
    {
      "key": "e_1_2_6_51_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jnr.490400215"
    },
    {
      "key": "e_1_2_6_52_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-4547(19970201)47:3<253::AID-JNR3>3.0.CO;2-H"
    }
  ],
  "container-title": "Journal of Neuroscience Research",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjnr.1064",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.1064",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        11,
        19
      ]
    ],
    "date-time": "2023-11-19T13:58:02Z",
    "timestamp": 1700402282000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/jnr.1064"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        3,
        29
      ]
    ]
  },
  "references-count": 51,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2001,
          4,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/jnr.1064"
  ],
  "URL": "http://dx.doi.org/10.1002/jnr.1064",
  "relation": {},
  "ISSN": [
    "0360-4012",
    "1097-4547"
  ],
  "subject": [],
  "container-title-short": "J of Neuroscience Research",
  "published": {
    "date-parts": [
      [
        2001,
        3,
        29
      ]
    ]
  }
}