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Role of the mitochondrial permeability transition and cytochrome C release in hydrogen peroxide-induced apoptosis.
Exp Cell Res. 2002 Mar 10; 274(1):16-24.EC

Abstract

We investigated the role of the mitochondrial inner membrane permeability transition and subsequent release of cytochrome c into the cytosol during oxidative stress-evoked apoptosis. Sublethal oxidative stress was applied by treating L929 cells with 0.5 mM H2O2 for 90 min. Then the cellular localization of cytochrome c was examined by immunofluorescent staining and Western blotting. H2O2 treatment caused the permeability transition and pore formation, resulting in membrane depolarization and translocation of cytochrome c from the mitochondria into the cytosol. Pretreatment with cyclosporin A and aristolochic acid (to inhibit pore formation) significantly attenuated a reduction of the mitochondrial membrane potential, as well as signs of apoptosis such as DNA fragmentation, increased plasma membrane permeability, and chromatin condensation. Therefore, exposure to H2O2 caused the opening of permeability transition pores in the inner mitochondrial membrane. An essential role of cytosolic cytochrome c in the execution of apoptosis was demonstrated by its direct microinjection into the cytosol, thus bypassing the need for cytochrome c release from the mitochondrial intermembrane space. Microinjection of cytochrome c caused caspase-dependent apoptosis.

Authors+Show Affiliations

Department of Emergency and Critical Care Medicine, Kansai Medical University, Fumizono-cho 10-15, Moriguchi, Osaka, 570-8507, Japan. takeyama@takii.kmu.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11855853

Citation

Takeyama, N, et al. "Role of the Mitochondrial Permeability Transition and Cytochrome C Release in Hydrogen Peroxide-induced Apoptosis." Experimental Cell Research, vol. 274, no. 1, 2002, pp. 16-24.
Takeyama N, Miki S, Hirakawa A, et al. Role of the mitochondrial permeability transition and cytochrome C release in hydrogen peroxide-induced apoptosis. Exp Cell Res. 2002;274(1):16-24.
Takeyama, N., Miki, S., Hirakawa, A., & Tanaka, T. (2002). Role of the mitochondrial permeability transition and cytochrome C release in hydrogen peroxide-induced apoptosis. Experimental Cell Research, 274(1), 16-24.
Takeyama N, et al. Role of the Mitochondrial Permeability Transition and Cytochrome C Release in Hydrogen Peroxide-induced Apoptosis. Exp Cell Res. 2002 Mar 10;274(1):16-24. PubMed PMID: 11855853.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the mitochondrial permeability transition and cytochrome C release in hydrogen peroxide-induced apoptosis. AU - Takeyama,N, AU - Miki,S, AU - Hirakawa,A, AU - Tanaka,T, PY - 2002/2/22/pubmed PY - 2002/4/19/medline PY - 2002/2/22/entrez SP - 16 EP - 24 JF - Experimental cell research JO - Exp Cell Res VL - 274 IS - 1 N2 - We investigated the role of the mitochondrial inner membrane permeability transition and subsequent release of cytochrome c into the cytosol during oxidative stress-evoked apoptosis. Sublethal oxidative stress was applied by treating L929 cells with 0.5 mM H2O2 for 90 min. Then the cellular localization of cytochrome c was examined by immunofluorescent staining and Western blotting. H2O2 treatment caused the permeability transition and pore formation, resulting in membrane depolarization and translocation of cytochrome c from the mitochondria into the cytosol. Pretreatment with cyclosporin A and aristolochic acid (to inhibit pore formation) significantly attenuated a reduction of the mitochondrial membrane potential, as well as signs of apoptosis such as DNA fragmentation, increased plasma membrane permeability, and chromatin condensation. Therefore, exposure to H2O2 caused the opening of permeability transition pores in the inner mitochondrial membrane. An essential role of cytosolic cytochrome c in the execution of apoptosis was demonstrated by its direct microinjection into the cytosol, thus bypassing the need for cytochrome c release from the mitochondrial intermembrane space. Microinjection of cytochrome c caused caspase-dependent apoptosis. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/11855853/Role_of_the_mitochondrial_permeability_transition_and_cytochrome_C_release_in_hydrogen_peroxide_induced_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014482701954473 DB - PRIME DP - Unbound Medicine ER -