DOI: 10.1111/j.1365-2796.1995.tb00881.x. Apoptosis: molecular mechanisms and implications for human disease

Apoptosis: molecular mechanisms and implications for human disease

10.1111/j.1365-2796.1995.tb00881.x

Crossref journal-article

Wiley

Journal of Internal Medicine (311)

Abstract

Abstract. Apoptosis is a highly regulated process of cell death with characteristic morphological changes that are distinct from necrosis. The biochemical machinery responsible for apoptotic cell death appears to be constitutively expressed in most, if not all, cells and can be triggered by a variety of signals, including sustained increases in the intracellular Ca2+ level. Apoptosis is the main mechanism of cell deletion during development, normal cell turnover, hormone‐induced tissue atrophy, and pathological processes such as T‐cell depletion in HIV/AIDS and neurodegenerative disease. The aim of this review is to briefly summarize current knowledge of the molecular mechanisms of apoptosis and its role in human disease.

Bibliography

ORRENIUS, S. (1995). Apoptosis: molecular mechanisms and implications for human disease. Journal of Internal Medicine, 237(6), 529â536. Portico.

Authors 1

STEN ORRENIUS (first)

References 60 Referenced 73

10.1016/S0074-7696(08)62312-8
10.1038/284555a0
10.1016/0006-291X(73)90740-7
10.1016/S0021-9258(18)33615-9 / J Biol Chem / Endogenous nuclease: properties and effects on transcribed genes in chromatin by Vanderbilt JN (1982)
10.4049/jimmunol.132.1.38
10.1016/0143-4160(94)90091-4
10.1016/S0021-9258(18)53654-1
10.1016/0014-5793(94)00827-2
10.1002/j.1460-2075.1990.tb08241.x
10.1038/356397a0
10.1128/MCB.11.8.4177
{'key': 'e_1_2_1_13_2', 'first-page': '1915', 'article-title': 'Constitutive c‐myc expression in an IL‐3 dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis', 'volume': '6', 'author': 'Askew DS', 'year': '1991', 'journal-title': 'Oncogene'} / Oncogene / Constitutive c‐myc expression in an IL‐3 dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis by Askew DS (1991)
10.1016/0092-8674(92)90123-T
10.1126/science.1378649
10.1038/363166a0
10.1182/blood.V80.4.879.879
10.1128/MCB.12.6.2570
{'key': 'e_1_2_1_19_2', 'first-page': '1735', 'article-title': 'Activation of the ableson tyrosine kinase activity is associated with supression of apoptosis in hemopoietic cells', 'volume': '53', 'author': 'Evans CA', 'year': '1993', 'journal-title': 'Cancer Res'} / Cancer Res / Activation of the ableson tyrosine kinase activity is associated with supression of apoptosis in hemopoietic cells by Evans CA (1993)
10.1038/356494a0
10.1126/science.1470921
10.1038/358015a0
10.1038/352345a0
10.1038/362847a0
10.1038/362849a0
10.1016/0962-8924(94)90087-6
10.1073/pnas.74.2.638
10.1016/0003-9861(89)90119-7
10.1084/jem.167.2.514
10.1096/fasebj.4.9.2347464
10.1038/337181a0
10.4049/jimmunol.143.6.1801 / J Immunol / Calcium‐dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex by McConkey DJ (1989)
10.1002/pros.2990170302
10.1126/science.7686306
10.1016/S0021-9258(17)44906-4 / J Biol Chem / Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and Novobiocin by Alnemri ES (1990)
10.1002/j.1460-2075.1990.tb07492.x
10.4049/jimmunol.148.5.1416 / J. Immunol / Inhibition of apoptosis by calcium ionophores in IL‐3‐dependent bone marrow cells is dependent upon production of IL‐4 by Rodriguez‐Tarduchy G. (1992)
10.1016/0014-4827(91)90380-D
10.1042/bj2600697
10.1038/356314a0
10.1016/0167-5699(92)90066-G
10.1002/eji.1830240526
{'key': 'e_1_2_1_43_2', 'first-page': '205', 'article-title': 'Transcriptional overexpression of the protooncogene bcl‐2 in patients with systemic Lupus erythematosus', 'volume': '104', 'author': 'Graninger WB', 'year': '1992', 'journal-title': 'Wien Klin Wochenschr'} / Wien Klin Wochenschr / Transcriptional overexpression of the protooncogene bcl‐2 in patients with systemic Lupus erythematosus by Graninger WB (1992)
10.1172/JCI115188
10.1084/jem.175.2.331
10.1126/science.8098552
10.1126/science.2326646
{'key': 'e_1_2_1_48_2', 'first-page': '403', 'article-title': 'Deletion and depletion: the involvement of viruses and environmental factors in T‐lymphocyte apoptosis', 'volume': '66', 'author': 'McCabe MJ', 'year': '1992', 'journal-title': 'Lab Invest'} / Lab Invest / Deletion and depletion: the involvement of viruses and environmental factors in T‐lymphocyte apoptosis by McCabe MJ (1992)
10.1016/0167-5699(92)90156-2 / Immunol Today / HIV‐induced cysteine deficiency and T‐cell dysfunction ‐ a rationale for treatment with N‐acetylcysteine by Dröge W. (1992)
10.1073/pnas.91.9.3619
10.1111/j.1749-6632.1992.tb38643.x
10.1016/0014-5793(92)80885-K
10.1073/pnas.90.17.7951
10.1038/362543a0
10.1016/0006-291X(91)91330-F
10.1073/pnas.90.10.4533
{'key': 'e_1_2_1_57_2', 'first-page': '1045', 'article-title': 'Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes', 'volume': '144', 'author': 'Arends MJ', 'year': '1994', 'journal-title': 'Am J Path'} / Am J Path / Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes by Arends MJ (1994)
10.1096/fasebj.8.9.8005393
10.1007/BF00048059
10.1002/path.1711160302
10.1182/blood.V81.1.143.143 / Blood / Induction of apoptotic cell death in chronic lymphcytic leukemia by 2‐chloro‐2′‐deoxyadenosine and 9‐beta‐D‐arabinosyl‐2′‐fluroadenine by Robertson LE (1993)

Dates

Type	When
Created	16 years, 1 month ago (Aug. 4, 2009, 5:25 a.m.)
Deposited	1 year, 10 months ago (Oct. 25, 2023, 8:44 p.m.)
Indexed	3 months, 1 week ago (May 24, 2025, 9:49 p.m.)
Issued	30 years, 3 months ago (June 1, 1995)
Published	30 years, 3 months ago (June 1, 1995)
Published Online	16 years, 1 month ago (Aug. 4, 2009)
Published Print	30 years, 3 months ago (June 1, 1995)

Funders 0

None

BibTeX

@article{ORRENIUS_1995, title={Apoptosis: molecular mechanisms and implications for human disease}, volume={237}, ISSN={1365-2796}, url={http://dx.doi.org/10.1111/j.1365-2796.1995.tb00881.x}, DOI={10.1111/j.1365-2796.1995.tb00881.x}, number={6}, journal={Journal of Internal Medicine}, publisher={Wiley}, author={ORRENIUS, STEN}, year={1995}, month=jun, pages={529–536} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        5,
        25
      ]
    ],
    "date-time": "2025-05-25T01:49:46Z",
    "timestamp": 1748137786170
  },
  "reference-count": 60,
  "publisher": "Wiley",
  "issue": "6",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2009,
            8,
            4
          ]
        ],
        "date-time": "2009-08-04T00:00:00Z",
        "timestamp": 1249344000000
      },
      "content-version": "vor",
      "delay-in-days": 5178,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1995,
        6
      ]
    ]
  },
  "abstract": "<jats:p><jats:bold>Abstract. </jats:bold> Apoptosis is a highly regulated process of cell death with characteristic morphological changes that are distinct from necrosis. The biochemical machinery responsible for apoptotic cell death appears to be constitutively expressed in most, if not all, cells and can be triggered by a variety of signals, including sustained increases in the intracellular Ca<jats:sup>2+</jats:sup> level. Apoptosis is the main mechanism of cell deletion during development, normal cell turnover, hormone\u2010induced tissue atrophy, and pathological processes such as T\u2010cell depletion in HIV/AIDS and neurodegenerative disease. The aim of this review is to briefly summarize current knowledge of the molecular mechanisms of apoptosis and its role in human disease.</jats:p>",
  "DOI": "10.1111/j.1365-2796.1995.tb00881.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2009,
        8,
        4
      ]
    ],
    "date-time": "2009-08-04T09:25:10Z",
    "timestamp": 1249377910000
  },
  "page": "529-536",
  "source": "Crossref",
  "is-referenced-by-count": 73,
  "title": "Apoptosis: molecular mechanisms and implications for human disease",
  "prefix": "10.1111",
  "volume": "237",
  "author": [
    {
      "given": "STEN",
      "family": "ORRENIUS",
      "sequence": "first",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2009,
        8,
        4
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0074-7696(08)62312-8"
    },
    {
      "key": "e_1_2_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/284555a0"
    },
    {
      "key": "e_1_2_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-291X(73)90740-7"
    },
    {
      "key": "e_1_2_1_5_2",
      "doi-asserted-by": "crossref",
      "first-page": "13009",
      "DOI": "10.1016/S0021-9258(18)33615-9",
      "article-title": "Endogenous nuclease: properties and effects on transcribed genes in chromatin",
      "volume": "257",
      "author": "Vanderbilt JN",
      "year": "1982",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "e_1_2_1_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.132.1.38"
    },
    {
      "key": "e_1_2_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0143-4160(94)90091-4"
    },
    {
      "key": "e_1_2_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)53654-1"
    },
    {
      "key": "e_1_2_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(94)00827-2"
    },
    {
      "key": "e_1_2_1_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb08241.x"
    },
    {
      "key": "e_1_2_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/356397a0"
    },
    {
      "key": "e_1_2_1_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.11.8.4177"
    },
    {
      "key": "e_1_2_1_13_2",
      "first-page": "1915",
      "article-title": "Constitutive c\u2010myc expression in an IL\u20103 dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis",
      "volume": "6",
      "author": "Askew DS",
      "year": "1991",
      "journal-title": "Oncogene"
    },
    {
      "key": "e_1_2_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90123-T"
    },
    {
      "key": "e_1_2_1_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1378649"
    },
    {
      "key": "e_1_2_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/363166a0"
    },
    {
      "key": "e_1_2_1_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V80.4.879.879"
    },
    {
      "key": "e_1_2_1_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.12.6.2570"
    },
    {
      "key": "e_1_2_1_19_2",
      "first-page": "1735",
      "article-title": "Activation of the ableson tyrosine kinase activity is associated with supression of apoptosis in hemopoietic cells",
      "volume": "53",
      "author": "Evans CA",
      "year": "1993",
      "journal-title": "Cancer Res"
    },
    {
      "key": "e_1_2_1_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/356494a0"
    },
    {
      "key": "e_1_2_1_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1470921"
    },
    {
      "key": "e_1_2_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/358015a0"
    },
    {
      "key": "e_1_2_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/352345a0"
    },
    {
      "key": "e_1_2_1_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/362847a0"
    },
    {
      "key": "e_1_2_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/362849a0"
    },
    {
      "key": "e_1_2_1_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0962-8924(94)90087-6"
    },
    {
      "key": "e_1_2_1_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.74.2.638"
    },
    {
      "key": "e_1_2_1_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0003-9861(89)90119-7"
    },
    {
      "key": "e_1_2_1_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.167.2.514"
    },
    {
      "key": "e_1_2_1_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1096/fasebj.4.9.2347464"
    },
    {
      "key": "e_1_2_1_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/337181a0"
    },
    {
      "key": "e_1_2_1_32_2",
      "doi-asserted-by": "crossref",
      "first-page": "1801",
      "DOI": "10.4049/jimmunol.143.6.1801",
      "article-title": "Calcium\u2010dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex",
      "volume": "143",
      "author": "McConkey DJ",
      "year": "1989",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_2_1_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/pros.2990170302"
    },
    {
      "key": "e_1_2_1_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7686306"
    },
    {
      "key": "e_1_2_1_35_2",
      "doi-asserted-by": "crossref",
      "first-page": "17323",
      "DOI": "10.1016/S0021-9258(17)44906-4",
      "article-title": "Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and Novobiocin",
      "volume": "265",
      "author": "Alnemri ES",
      "year": "1990",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "e_1_2_1_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb07492.x"
    },
    {
      "key": "e_1_2_1_37_2",
      "doi-asserted-by": "crossref",
      "first-page": "1416",
      "DOI": "10.4049/jimmunol.148.5.1416",
      "article-title": "Inhibition of apoptosis by calcium ionophores in IL\u20103\u2010dependent bone marrow cells is dependent upon production of IL\u20104",
      "volume": "148",
      "author": "Rodriguez\u2010Tarduchy G.",
      "year": "1992",
      "journal-title": "J. Immunol"
    },
    {
      "key": "e_1_2_1_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-4827(91)90380-D"
    },
    {
      "key": "e_1_2_1_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj2600697"
    },
    {
      "key": "e_1_2_1_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/356314a0"
    },
    {
      "key": "e_1_2_1_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0167-5699(92)90066-G"
    },
    {
      "key": "e_1_2_1_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/eji.1830240526"
    },
    {
      "key": "e_1_2_1_43_2",
      "first-page": "205",
      "article-title": "Transcriptional overexpression of the protooncogene bcl\u20102 in patients with systemic Lupus erythematosus",
      "volume": "104",
      "author": "Graninger WB",
      "year": "1992",
      "journal-title": "Wien Klin Wochenschr"
    },
    {
      "key": "e_1_2_1_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI115188"
    },
    {
      "key": "e_1_2_1_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.175.2.331"
    },
    {
      "key": "e_1_2_1_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8098552"
    },
    {
      "key": "e_1_2_1_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2326646"
    },
    {
      "key": "e_1_2_1_48_2",
      "first-page": "403",
      "article-title": "Deletion and depletion: the involvement of viruses and environmental factors in T\u2010lymphocyte apoptosis",
      "volume": "66",
      "author": "McCabe MJ",
      "year": "1992",
      "journal-title": "Lab Invest"
    },
    {
      "key": "e_1_2_1_49_2",
      "doi-asserted-by": "crossref",
      "first-page": "211",
      "DOI": "10.1016/0167-5699(92)90156-2",
      "article-title": "HIV\u2010induced cysteine deficiency and T\u2010cell dysfunction \u2010 a rationale for treatment with N\u2010acetylcysteine",
      "volume": "13",
      "author": "Dr\u00f6ge W.",
      "year": "1992",
      "journal-title": "Immunol Today"
    },
    {
      "key": "e_1_2_1_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.9.3619"
    },
    {
      "key": "e_1_2_1_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1749-6632.1992.tb38643.x"
    },
    {
      "key": "e_1_2_1_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(92)80885-K"
    },
    {
      "key": "e_1_2_1_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.17.7951"
    },
    {
      "key": "e_1_2_1_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/362543a0"
    },
    {
      "key": "e_1_2_1_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-291X(91)91330-F"
    },
    {
      "key": "e_1_2_1_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.10.4533"
    },
    {
      "key": "e_1_2_1_57_2",
      "first-page": "1045",
      "article-title": "Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes",
      "volume": "144",
      "author": "Arends MJ",
      "year": "1994",
      "journal-title": "Am J Path"
    },
    {
      "key": "e_1_2_1_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1096/fasebj.8.9.8005393"
    },
    {
      "key": "e_1_2_1_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00048059"
    },
    {
      "key": "e_1_2_1_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/path.1711160302"
    },
    {
      "key": "e_1_2_1_61_2",
      "doi-asserted-by": "crossref",
      "first-page": "143",
      "DOI": "10.1182/blood.V81.1.143.143",
      "article-title": "Induction of apoptotic cell death in chronic lymphcytic leukemia by 2\u2010chloro\u20102\u2032\u2010deoxyadenosine and 9\u2010beta\u2010D\u2010arabinosyl\u20102\u2032\u2010fluroadenine",
      "volume": "81",
      "author": "Robertson LE",
      "year": "1993",
      "journal-title": "Blood"
    }
  ],
  "container-title": "Journal of Internal Medicine",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2796.1995.tb00881.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.1995.tb00881.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        26
      ]
    ],
    "date-time": "2023-10-26T00:44:53Z",
    "timestamp": 1698281093000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.1995.tb00881.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1995,
        6
      ]
    ]
  },
  "references-count": 60,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          1995,
          6
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1111/j.1365-2796.1995.tb00881.x"
  ],
  "URL": "http://dx.doi.org/10.1111/j.1365-2796.1995.tb00881.x",
  "relation": {},
  "ISSN": [
    "0954-6820",
    "1365-2796"
  ],
  "subject": [],
  "container-title-short": "Journal of Internal Medicine",
  "published": {
    "date-parts": [
      [
        1995,
        6
      ]
    ]
  }
}