DOI: 10.4049/jimmunol.165.5.2703. The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles

The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles

10.4049/jimmunol.165.5.2703

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract We are interested in the cytotoxic and proinflammatory effects of particulate pollutants in the respiratory tract. We demonstrate that methanol extracts made from diesel exhaust particles (DEP) induce apoptosis and reactive oxygen species (ROS) in pulmonary alveolar macrophages and RAW 264.7 cells. The toxicity of these organic extracts mimics the cytotoxicity of the intact particles and could be suppressed by the synthetic sulfhydryl compounds, N-acetylcysteine and bucillamine. Because DEP-induced apoptosis follows cytochrome c release, we studied the effect of DEP chemicals on mitochondrially regulated death mechanisms. Crude DEP extracts induced ROS production and perturbed mitochondrial function before and at the onset of apoptosis. This mitochondrial perturbation follows an orderly sequence of events, which commence with a change in mitochondrial membrane potential, followed by cytochrome c release, development of membrane asymmetry (annexin V staining), and propidium iodide uptake. Structural damage to the mitochondrial inner membrane, evidenced by a decrease in cardiolipin mass, leads to O⨪2 generation and uncoupling of oxidative phosphorylation (decreased intracellular ATP levels). N-Acetylcysteine reversed these mitochondrial effects and ROS production. Overexpression of the mitochondrial apoptosis regulator, Bcl-2, delayed but did not suppress apoptosis. Taken together, these results suggest that DEP chemicals induce apoptosis in macrophages via a toxic effect on mitochondria.

Bibliography

Hiura, T. S., Li, N., Kaplan, R., Horwitz, M., Seagrave, J.-C., & Nel, A. E. (2000). The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles. The Journal of Immunology, 165(5), 2703â2711.

Authors 6

Timothy S. Hiura (first)
Ning Li (additional)
Roman Kaplan (additional)
Marcus Horwitz (additional)
Jean-Clare Seagrave (additional)
Andre E. Nel (additional)

References 56 Referenced 157

Dates

Type	When
Created	11 years, 4 months ago (April 22, 2014, 5:58 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 11:54 a.m.)
Indexed	4 days, 16 hours ago (Aug. 23, 2025, 1:10 a.m.)
Issued	24 years, 11 months ago (Sept. 1, 2000)
Published	24 years, 11 months ago (Sept. 1, 2000)
Published Print	24 years, 11 months ago (Sept. 1, 2000)

Funders 0

None

BibTeX

@article{Hiura_2000, title={The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles}, volume={165}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.165.5.2703}, DOI={10.4049/jimmunol.165.5.2703}, number={5}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Hiura, Timothy S. and Li, Ning and Kaplan, Roman and Horwitz, Marcus and Seagrave, Jean-Clare and Nel, Andre E.}, year={2000}, month=sep, pages={2703–2711} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        23
      ]
    ],
    "date-time": "2025-08-23T05:10:38Z",
    "timestamp": 1755925838791,
    "version": "3.32.0"
  },
  "reference-count": 56,
  "publisher": "Oxford University Press (OUP)",
  "issue": "5",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        9,
        1
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>We are interested in the cytotoxic and proinflammatory effects of particulate pollutants in the respiratory tract. We demonstrate that methanol extracts made from diesel exhaust particles (DEP) induce apoptosis and reactive oxygen species (ROS) in pulmonary alveolar macrophages and RAW 264.7 cells. The toxicity of these organic extracts mimics the cytotoxicity of the intact particles and could be suppressed by the synthetic sulfhydryl compounds, N-acetylcysteine and bucillamine. Because DEP-induced apoptosis follows cytochrome c release, we studied the effect of DEP chemicals on mitochondrially regulated death mechanisms. Crude DEP extracts induced ROS production and perturbed mitochondrial function before and at the onset of apoptosis. This mitochondrial perturbation follows an orderly sequence of events, which commence with a change in mitochondrial membrane potential, followed by cytochrome c release, development of membrane asymmetry (annexin V staining), and propidium iodide uptake. Structural damage to the mitochondrial inner membrane, evidenced by a decrease in cardiolipin mass, leads to O\u2a2a2 generation and uncoupling of oxidative phosphorylation (decreased intracellular ATP levels). N-Acetylcysteine reversed these mitochondrial effects and ROS production. Overexpression of the mitochondrial apoptosis regulator, Bcl-2, delayed but did not suppress apoptosis. Taken together, these results suggest that DEP chemicals induce apoptosis in macrophages via a toxic effect on mitochondria.</jats:p>",
  "DOI": "10.4049/jimmunol.165.5.2703",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2014,
        4,
        22
      ]
    ],
    "date-time": "2014-04-22T21:58:09Z",
    "timestamp": 1398203889000
  },
  "page": "2703-2711",
  "source": "Crossref",
  "is-referenced-by-count": 157,
  "title": "The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles",
  "prefix": "10.1093",
  "volume": "165",
  "author": [
    {
      "given": "Timothy S.",
      "family": "Hiura",
      "sequence": "first",
      "affiliation": [
        {
          "name": "*Division of Clinical Immunology and Allergy and"
        }
      ]
    },
    {
      "given": "Ning",
      "family": "Li",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*Division of Clinical Immunology and Allergy and"
        }
      ]
    },
    {
      "given": "Roman",
      "family": "Kaplan",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*Division of Clinical Immunology and Allergy and"
        }
      ]
    },
    {
      "given": "Marcus",
      "family": "Horwitz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "\u2020Division of Infectious Diseases, Department of Medicine, University of California Medical School, Los Angeles, CA 90095; and"
        }
      ]
    },
    {
      "given": "Jean-Clare",
      "family": "Seagrave",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "\u2021Pathophysiology Division, Lovelace Respiratory Research Institute, Albuquerque, NM 87185"
        }
      ]
    },
    {
      "given": "Andre E.",
      "family": "Nel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*Division of Clinical Immunology and Allergy and"
        }
      ]
    }
  ],
  "member": "286",
  "reference": [
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Pope, C. A.,  M. J. Thun,  M. M. Namboodiri,  D. W. Dockery,  J. S. Evans,  F. E. Speizer,  C. W. Heath, Jr.  1995. Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. Am. J. Respir. Crit. Care Med.\u2008151: 669",
      "key": "2022123115355473100_R1",
      "DOI": "10.1164/ajrccm.151.3.7881654"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Dockery, D. W.,  C. A. Pope,  X. Xu,  J. D. Spengler,  J. H. Ware,  M. E. Fay,  B. G. Ferris,  F. E. Speizer.  1993. An association between air pollution and mortality in six U.S. cities. N. Engl. J. Med.\u200829: 1753",
      "key": "2022123115355473100_R2",
      "DOI": "10.1056/NEJM199312093292401"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Pope, C. A.,  D. W. Dockery.  1998. Epidemiology of particle effects.  S. T. Holgate, Jr, and J. M. Samet, Jr, and H. S. Koren, Jr, and R. L. Maynard, Jr,  eds. Air Pollution and Health\u2008673 Academic Press,  London.",
      "key": "2022123115355473100_R3",
      "DOI": "10.1016/B978-012352335-8/50106-X"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Pope, C. A..  1999. Mortality and air pollution: associations persist with continued advances in research methodology. Environ. Health Perspect.\u2008107: 613",
      "key": "2022123115355473100_R4",
      "DOI": "10.2307/3434450"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Pope, C. A.,  D. W. Dockery,  R. E. Kanner,  G. M. Villegas,  J. Schwartz.  1999. Oxygen saturation, pulse rate, and particulate air pollution: a daily time-series panel study. Am. J. Respir. Crit. Care Med.\u2008159: 365",
      "key": "2022123115355473100_R5",
      "DOI": "10.1164/ajrccm.159.2.9702103"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Sagai, M.,  H. Saito,  T. Ichinose,  M. Kodama,  Y. Morri.  1993. Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse. Free Radical Biol. Med.\u200814: 37",
      "key": "2022123115355473100_R6",
      "DOI": "10.1016/0891-5849(93)90507-Q"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Ichinose, T.,  A. Furuyama,  M. Sagai.  1995. Biological effects of diesel exhaust particles (DEP). II. Acute toxicity of DEP introduced into lung by intratracheal instillation. Toxicology\u200899: 153",
      "key": "2022123115355473100_R7",
      "DOI": "10.1016/0300-483X(94)03013-R"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Alsberg, T.,  U. Stenberg,  R. Westerholm,  M. Strandell,  U. Rannug,  A. Sundvall,  L. Romert,  U. Bernson,  B. Petersson,  R. Toftgard, et al\u20081985. Chemical and biological characterization of organic material from gasoline exhaust particles. Environ. Sci. Technol.\u200819: 43",
      "key": "2022123115355473100_R8",
      "DOI": "10.1021/es00131a003"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Schuetzle, D.,  F. S. Lee,  J. J. Prater.  1981. The identification of polynuclear aromatic hydrocarbon (PAH) derivatives in mutagenic fractions of diesel particulate extracts. Int. J. Environ. Anal. Chem.\u20089: 93",
      "key": "2022123115355473100_R9",
      "DOI": "10.1080/03067318108071903"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Li, H.,  C. D. Banner,  G. G. Mason,  R. N. Westerholm,  J. J. Rafter.  1996. Determination of polycyclic aromatic compounds and dioxan receptor ligands present in diesel exhaust particulate extracts. Atmos. Environ.\u200830: 3537",
      "key": "2022123115355473100_R10",
      "DOI": "10.1016/1352-2310(96)00051-9"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Andersson, H.,  E. Lindqvist,  R. Westerholm,  K. Gragg,  J. Almen,  L. Olson.  1998. Neurotoxic effects of fractionated diesel exhaust following microinjections in rat hippocampus and striatum. Environ. Res.\u200876: 41",
      "key": "2022123115355473100_R11",
      "DOI": "10.1006/enrs.1997.3791"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Kumagai, Y.,  T. Arimoto,  M. Shinyashiki,  N. Shimojo,  Y. Nakai,  T. Yoshikawa,  M. Sagai.  1997. Generation of reactive oxygen species during interaction of diesel exhaust particle components with NADPH-cytochrome P450 reductase and involvement of the bioactivation in the DNA damage. Free Radical Biol. Med.\u200822: 479",
      "key": "2022123115355473100_R12",
      "DOI": "10.1016/S0891-5849(96)00341-3"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Sagai, M.,  A. Furuyama,  T. Ichinose.  1996. Biological effects of diesel exhaust particles (DEP). III. Pathogenesis of asthma-like symptoms in mice. Free Radical Biol. Med.\u200821: 199",
      "key": "2022123115355473100_R13",
      "DOI": "10.1016/0891-5849(96)00032-9"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Lim, H. B.,  T. Ichinose,  Y. Miyabara,  H. Takano,  Y. Kumagai,  N. Shimojyo,  J. L. Devalia,  M. Sagai.  1998. Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice. Free Radical Biol Med.\u200825: 635",
      "key": "2022123115355473100_R14",
      "DOI": "10.1016/S0891-5849(98)00073-2"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "MacNee, W.,  K. Donaldson.  1998. Particulate air pollution: injurious and protective mechanisms in the lung.  S. T. Holgate, Jr, and J. M. Samet, Jr, and H. S. Koren, Jr, and R. L. Maynard, Jr,  eds. Air Pollution and Health\u2008653 Academic Press,  London.",
      "key": "2022123115355473100_R15",
      "DOI": "10.1016/B978-012352335-8/50105-8"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Nel, A. E,  D. Diaz-Sanchez,  D. Ng,  T. Hiura,  A. Saxon.  1998. Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. J. Allergy Clin. Immunol.\u2008102: 539",
      "key": "2022123115355473100_R16",
      "DOI": "10.1016/S0091-6749(98)70269-6"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Becker, S.,  J. M. Soukup,  M. I. Gilmour,  R. B. Devlin.  1996. Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. Toxicol. Appl. Pharmacol.\u2008141: 637",
      "key": "2022123115355473100_R17",
      "DOI": "10.1006/taap.1996.0330"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Goldsmith, C.,  C. Frevert,  A. Imrich,  C. Sioutas,  L. Kobzik.  1997. Alveolar macrophage interaction with air pollution particulates. Environ. Health Perspect.\u2008105: 1191",
      "key": "2022123115355473100_R18",
      "DOI": "10.2307/3433531"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Hiura, T. S.,  M. Kaszubowski,  N. Li,  A. E. Nel.  1999. Chemicals in diesel exhaust particles generate reactive oxygen radicals and apoptosis in macrophages. J. Immunol.\u2008163: 5582",
      "key": "2022123115355473100_R19",
      "DOI": "10.4049/jimmunol.163.10.5582"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Foster, W. M..  1998. Deposition and clearance of inhaled particles.  S.T. Holgate, Jr, and J.M. Samet, Jr, and H.S. Koren, Jr, and R.L. Maynard, Jr,  eds. Air Pollution and Health\u2008295 Academic Press,  London.",
      "key": "2022123115355473100_R20",
      "DOI": "10.1016/B978-012352335-8/50089-2"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Cohen, A. J.,  K. Nikula.  1998. The health effects of diesel exhaust: laboratory and epidemiologic studies.  S. T. Holgate, Jr, and J. M. Samet, Jr, and H. S. Koren, Jr, and R. L. Maynard, Jr,  eds. Air Pollution and Health\u2008707 Academic Press,  London.",
      "key": "2022123115355473100_R21",
      "DOI": "10.1016/B978-012352335-8/50107-1"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "McLemore, T. L.,  R. R. Martin,  K. L. Toppell,  D. L. Busbee,  E. T. Cantrell.  1997. Comparison of aryl hydrocarbon hydroxylase in cultured blood lymphocytes and pulmonary macrophages. J. Clin. Invest.\u200860: 1017",
      "key": "2022123115355473100_R22",
      "DOI": "10.1172/JCI108852"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Harris, C. C.,  I. C. Hsu,  G. D. Stoner,  B. F. Trump,  J. K. Selkirk.  1978. Human pulmonary alveolar macrophages metabolize benzo(a)pyrene to proximate and ultimate mutagens. Nature\u2008272: 633",
      "key": "2022123115355473100_R23",
      "DOI": "10.1038/272633a0"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Hayashi, S.,  J. Okabe-Kado,  Y. Honma,  K. Kawajiri.  1995. Expression of Ah receptor (TCDD receptor) during human monocytic differentiation. Carcinogenesis\u200816: 1403",
      "key": "2022123115355473100_R24",
      "DOI": "10.1093/carcin/16.6.1403"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Susin, S. A.,  N. Zamzami,  G. Kroemer.  1998. Mitochondria as regulators of apoptosis: doubt no more. Biochim. Biophys. Acta\u20081366: 151",
      "key": "2022123115355473100_R25",
      "DOI": "10.1016/S0005-2728(98)00110-8"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Hirsch, T.,  P. Marchetti,  S. A. Susin,  B. Dallaporta,  N. Zamzami,  I. Marzo,  M. Geuskens,  G. Kroemer.  1997. The apoptosis-necrosis paradox: apoptogenic proteases activated after mitochondrial permeability transition determine the mode of cell death. Oncogene\u200815: 1573",
      "key": "2022123115355473100_R26",
      "DOI": "10.1038/sj.onc.1201324"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Green, D. R.,  J. C. Reed.  1998. Mitochondria and apoptosis. Science\u2008281: 1309",
      "key": "2022123115355473100_R27",
      "DOI": "10.1126/science.281.5381.1309"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Cai, J.,  J. Yang,  D. P. Jones.  1998. Mitochondrial control of apoptosis: the role of cytochrome c. Biochim. Biophys. Acta\u20081366: 139",
      "key": "2022123115355473100_R28",
      "DOI": "10.1016/S0005-2728(98)00109-1"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Zoratti, M.,  I. Szabo.  1995. The mitochondrial permeability transition. Biochim. Biophys. Acta\u20081241: 139",
      "key": "2022123115355473100_R29",
      "DOI": "10.1016/0304-4157(95)00003-A"
    },
    {
      "unstructured": "Jajte, J. M..  1997. Chemical-induced changes in intracellular redox state and in apoptosis. Int. J. Occup. Med. Environ. Health\u200810: 203",
      "key": "2022123115355473100_R30"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Kowaltowski, A. J.,  A. E. Vercesi.  1999. Mitochondrial damage induced by conditions of oxidative stress. Free Radical Biol. Med.\u200826: 463",
      "key": "2022123115355473100_R31",
      "DOI": "10.1016/S0891-5849(98)00216-0"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Kroemer, G.,  B. Dallaporta,  M. Resche-Rigon.  1998. The mitochondrial death/life regulator in apoptosis and necrosis. Annu. Rev. Physiol.\u200860: 619",
      "key": "2022123115355473100_R32",
      "DOI": "10.1146/annurev.physiol.60.1.619"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Petit, P. X.,  J. E. O\u2019Connor,  D. Grunwald,  S. C. Brown.  1990. Analysis of the membrane potential of rat- and mouse-liver mitochondria by flow cytometry and possible applications. Eur. J. Biochem.\u2008194: 389",
      "key": "2022123115355473100_R33",
      "DOI": "10.1111/j.1432-1033.1990.tb15632.x"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Rothe, G.,  G. Valet.  1990. Flow cytometric analysis of respiratory burst activity in phagocytoes with hydroethidine and 2\u2032,7\u2032-dichlorofluorescin. J. Leukocyte Biol.\u200847: 440",
      "key": "2022123115355473100_R34",
      "DOI": "10.1002/jlb.47.5.440"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Petit, J. M.,  A. Maftah,  M. H. Ratinaud,  R. Julien.  1992. 10 N-nonylacridine orange interacts with cardiolipin and allows for the quantification of phospholipids in isolated mitochondria. Eur. J. Biochem.\u2008209: 267",
      "key": "2022123115355473100_R35",
      "DOI": "10.1111/j.1432-1033.1992.tb17285.x"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Gossen, M.,  H. Bujard.  1992. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA\u200889: 5547",
      "key": "2022123115355473100_R36",
      "DOI": "10.1073/pnas.89.12.5547"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Faris, M.,  N. Kokot,  L. Lee,  A. E. Nel.  1996. Regulation of interleukin-2 transcription by inducible stable expression of dominant-negative and dominant-active mitogen-activated protein kinase kinase kinase in Jurkat T cells. J. Biol. Chem.\u2008271: 27366",
      "key": "2022123115355473100_R37",
      "DOI": "10.1074/jbc.271.44.27366"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Nagaishi, K.,  R. Adachi,  S. Matsui,  T. Yamaguchi,  T. Kasahara,  K. Suzuki.  1999. Herbimycin A inhibits both dephosphorylation and translocation of cofilin induced by opsonized zymosan in macrophagelike U937 cells. J. Cell. Physiol.\u2008180: 345",
      "key": "2022123115355473100_R38",
      "DOI": "10.1002/(SICI)1097-4652(199909)180:3<345::AID-JCP5>3.0.CO;2-J"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Rauen, U.,  I. Reuters,  A. Fuchs,  H. de Groot.  1997. Oxygen-free radical-mediated injury to cold rat hepatocytes during cold incubation in preservation solutions. Hepatology\u200826: 351",
      "key": "2022123115355473100_R39",
      "DOI": "10.1002/hep.510260215"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Brown, J. E.,  H. Khodr,  R. C. Hider,  C. A. Rice-Evans.  1998. Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties. Biochem. J.\u2008330: 1173",
      "key": "2022123115355473100_R40",
      "DOI": "10.1042/bj3301173"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Noroozi, M.,  W. J. Angerson,  M. E. Lean.  1998. Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Am. J. Clin. Nutr.\u200867: 1210",
      "key": "2022123115355473100_R41",
      "DOI": "10.1093/ajcn/67.6.1210"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Higuchi, M.,  R. J. Poske,  E. T. Yeh.  1998. Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene.\u200817: 2515",
      "key": "2022123115355473100_R42",
      "DOI": "10.1038/sj.onc.1202485"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Mignotte, B.,  G. Kroemer.  1995. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J. Exp. Med.\u2008182: 367",
      "key": "2022123115355473100_R43",
      "DOI": "10.1084/jem.182.2.367"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Reed, J. C.,  J. M. Jurgensmeier,  S. Matsuyama.  1998. Bcl-2 family proteins and mitochondria. Biochim. Biophys. Acta\u20081366: 127",
      "key": "2022123115355473100_R44",
      "DOI": "10.1016/S0005-2728(98)00108-X"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Kluck, R. M.,  E. Bossy-Wetzel,  D. R. Green,  D. D. Newmeyer.  1997. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science\u2008275: 1132",
      "key": "2022123115355473100_R45",
      "DOI": "10.1126/science.275.5303.1132"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Marzo, I.,  C. Brenner,  N. Zamzami,  S. A. Susin,  G. Beutner,  D. Brdiczka,  R. Remy,  Z. H. Xie,  J. C. Reed,  G. Kroemer.  1998. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J. Exp. Med.\u2008187: 1261",
      "key": "2022123115355473100_R46",
      "DOI": "10.1084/jem.187.8.1261"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Chesis, P. L.,  D. E. Levin,  M. T. Smith,  L. Ernster,  B. N. Ames.  1984. Mutagenicity of quinones: pathways of metabolic activation and detoxification. Proc. Natl. Acad. Sci. USA\u200881: 1696",
      "key": "2022123115355473100_R47",
      "DOI": "10.1073/pnas.81.6.1696"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Monks, T. J.,  R. P. Hanzlik,  G. M. Cohen,  D. Ross,  D. G. Graham.  1992. Quinone chemistry and toxicity. Toxicol. Appl. Pharmacol.\u2008112: 2",
      "key": "2022123115355473100_R48",
      "DOI": "10.1016/0041-008X(92)90273-U"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Thor, H.,  M. T. Smith,  P. Hartzell,  G. Bellomo,  S. A. Jewell,  S. Orrenius.  1982. The metabolism of menadione (2-methyl-1,4-napthoquinone) by isolated hepatocytes: a study in the implication of oxidative stress in intact cells. J. Biol. Chem.\u2008257: 12419",
      "key": "2022123115355473100_R49",
      "DOI": "10.1016/S0021-9258(18)33730-X"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Ghio, A. J.,  J. M. Samet.  1998. Metals and air pollution particles.  S. T. Holgate, Jr, and J. M. Samet, Jr, and H. S. Koren, Jr, and R. L. Maynard, Jr,  eds. Air Pollution and Health\u2008653 Academic Press,  London.",
      "key": "2022123115355473100_R50",
      "DOI": "10.1016/B978-012352335-8/50104-6"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Segura-Aguilar, J.,  D. Metodiewa,  C. J. Welch.  1998. Metabolic activation of dopamine o-quinones to o-semiquinones by NADPH cytochrome p450 reductase may play an important role in oxidative stress and apoptotic effects. Biochim. Biophys. Acta\u20081381: 1",
      "key": "2022123115355473100_R51",
      "DOI": "10.1016/S0304-4165(98)00036-1"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Yamaguchi, K.,  R. Near,  A. Sihneider,  H. Culi,  S. Ju,  D. H. Sherr.  1996. Fluoranthene-induced apoptosis in murine T cell hybridomas is independent of the aromatic hydrocarbon receptor. Toxicol. Appl. Pharmacol.\u2008139: 144",
      "key": "2022123115355473100_R52",
      "DOI": "10.1006/taap.1996.0153"
    },
    {
      "unstructured": "Lei, W.,  R. Yu,  S. Mandlekar,  A. T. Kong.  1998. Induction of apoptosis and activation of interleukin 1\u03b2-converting enzyme/Ced-3 protease (caspase-3) and c-Jun NH2-terminal kinase 1 by benzo(a)pyrene. Cancer Res.\u200858: 2102",
      "key": "2022123115355473100_R53"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Hahon, N.,  J. A. Booth,  F. Green,  T. R. Lewis.  1985. Influenza virus infection in mice after exposure to coal dust and diesel engine emissions. Environ. Res.\u200837: 44",
      "key": "2022123115355473100_R54",
      "DOI": "10.1016/0013-9351(85)90048-9"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Creutzenberg, O.,  B. Bellmann,  U. Heinrich.  1990. Clearance and retention of inhaled diesel exhaust particles, carbon black and titanium oxide in rats at lung overload conditions. J. Aerosol Med.\u200821: 455",
      "key": "2022123115355473100_R55",
      "DOI": "10.1016/0021-8502(90)90279-7"
    },
    {
      "doi-asserted-by": "crossref",
      "unstructured": "Martin, L. D.,  T. M. Krunkosky,  J. A. Dye,  B. M. Fischer,  N. F. Jiang,  L. G. Rochelle,  N. J. Akley,  K. L. Dreber,  K. B. Adler.  1997. The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates. Environ. Health Perspect.\u2008105: 1301",
      "key": "2022123115355473100_R56",
      "DOI": "10.2307/3433551"
    }
  ],
  "container-title": "The Journal of Immunology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/165/5/2703/1122794/2703.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/165/5/2703/1122794/2703.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        1,
        2
      ]
    ],
    "date-time": "2025-01-02T16:54:44Z",
    "timestamp": 1735836884000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.aai.org/jimmunol/article/165/5/2703/33196/The-Role-of-a-Mitochondrial-Pathway-in-the"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        9,
        1
      ]
    ]
  },
  "references-count": 56,
  "journal-issue": {
    "issue": "5",
    "published-print": {
      "date-parts": [
        [
          2000,
          9,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.4049/jimmunol.165.5.2703",
  "relation": {},
  "ISSN": [
    "0022-1767",
    "1550-6606"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2000,
        9,
        1
      ]
    ]
  }
}