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Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage induced by transforming growth factor beta1.

Abstract

Apoptosis is an important cell suicide program which involves the caspases activation and is implicated in physiological and pathological processes. Poly(ADP-ribose) polymerase (PARP) cleavage is often associated with apoptosis and has been served as one hallmark of apoptosis and caspase activation. In this study, we aimed to determine TGF-beta1-induced apoptosis and to examine the involvement of caspases and its relationship with PARP cleavage. TGF-beta1 induces strong apoptosis of AML-12 cells which can be detected by DNA fragmentation, FACS, and morphological assays. Z-VAD-fmk, a selective caspase inhibitor, partially inhibits the TGF-beta1-induced apoptosis; but has no effect on TGF-beta1-induced DNA fragmentation and PARP cleavage. However, BD-fmk, a broad-spectrum caspase inhibitor, completely suppresses TGF-beta1-induced apoptosis, but unexpectedly does not inhibit TGF-beta1-induced PARP cleavage. Furthermore, Z-VAD-fmk treatment is able to completely inhibit the daunorubicin-induced apoptosis in A-431 cells, but only slightly blocks the daunorubicin-induced PARP cleavage, whereas BD-fmk can inhibit both daunorubicin-induced apoptosis and PARP cleavage completely. In addition, we observed that both TGF-beta1-induced apoptosis and PARP degradation in AML-12 cells can be completely blocked by inhibiting the protein synthesis with cycloheximide. These results demonstrate for the first time that TGF-beta1-induced caspase-dependent apoptosis is associated with caspase-independent PARP cleavage that requires the TGF-beta1-induced synthesis of new proteins. The results indicate that caspase-3 is not a major caspase involved in TGF-beta1-induced apoptosis in AML-12 cells, and is not required for apoptosis-associated DNA fragmentation. The results also suggest that PARP cleavage may occur as an independent event that can be disassociated with cell apoptosis.

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  • Authors+Show Affiliations

    ,

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, 200031, Shanghai, China.

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    Source

    MeSH

    Amino Acid Chloromethyl Ketones
    Animals
    Apoptosis
    Caspases
    Cell Line
    Cell Separation
    Cycloheximide
    DNA Fragmentation
    Daunorubicin
    Enzyme Inhibitors
    Flow Cytometry
    Hepatocytes
    Immunoblotting
    Mice
    Microscopy, Fluorescence
    Poly(ADP-ribose) Polymerases
    Protein Kinase C
    Protein Kinase C-delta
    Protein Synthesis Inhibitors
    Time Factors
    Transforming Growth Factor beta
    Transforming Growth Factor beta1

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    14643888

    Citation

    Yang, Yanan, et al. "Caspase-dependent Apoptosis and -independent poly(ADP-ribose) Polymerase Cleavage Induced By Transforming Growth Factor Beta1." The International Journal of Biochemistry & Cell Biology, vol. 36, no. 2, 2004, pp. 223-34.
    Yang Y, Zhao S, Song J. Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage induced by transforming growth factor beta1. Int J Biochem Cell Biol. 2004;36(2):223-34.
    Yang, Y., Zhao, S., & Song, J. (2004). Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage induced by transforming growth factor beta1. The International Journal of Biochemistry & Cell Biology, 36(2), pp. 223-34.
    Yang Y, Zhao S, Song J. Caspase-dependent Apoptosis and -independent poly(ADP-ribose) Polymerase Cleavage Induced By Transforming Growth Factor Beta1. Int J Biochem Cell Biol. 2004;36(2):223-34. PubMed PMID: 14643888.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage induced by transforming growth factor beta1. AU - Yang,Yanan, AU - Zhao,Sheng, AU - Song,Jianguo, PY - 2003/12/4/pubmed PY - 2004/8/6/medline PY - 2003/12/4/entrez SP - 223 EP - 34 JF - The international journal of biochemistry & cell biology JO - Int. J. Biochem. Cell Biol. VL - 36 IS - 2 N2 - Apoptosis is an important cell suicide program which involves the caspases activation and is implicated in physiological and pathological processes. Poly(ADP-ribose) polymerase (PARP) cleavage is often associated with apoptosis and has been served as one hallmark of apoptosis and caspase activation. In this study, we aimed to determine TGF-beta1-induced apoptosis and to examine the involvement of caspases and its relationship with PARP cleavage. TGF-beta1 induces strong apoptosis of AML-12 cells which can be detected by DNA fragmentation, FACS, and morphological assays. Z-VAD-fmk, a selective caspase inhibitor, partially inhibits the TGF-beta1-induced apoptosis; but has no effect on TGF-beta1-induced DNA fragmentation and PARP cleavage. However, BD-fmk, a broad-spectrum caspase inhibitor, completely suppresses TGF-beta1-induced apoptosis, but unexpectedly does not inhibit TGF-beta1-induced PARP cleavage. Furthermore, Z-VAD-fmk treatment is able to completely inhibit the daunorubicin-induced apoptosis in A-431 cells, but only slightly blocks the daunorubicin-induced PARP cleavage, whereas BD-fmk can inhibit both daunorubicin-induced apoptosis and PARP cleavage completely. In addition, we observed that both TGF-beta1-induced apoptosis and PARP degradation in AML-12 cells can be completely blocked by inhibiting the protein synthesis with cycloheximide. These results demonstrate for the first time that TGF-beta1-induced caspase-dependent apoptosis is associated with caspase-independent PARP cleavage that requires the TGF-beta1-induced synthesis of new proteins. The results indicate that caspase-3 is not a major caspase involved in TGF-beta1-induced apoptosis in AML-12 cells, and is not required for apoptosis-associated DNA fragmentation. The results also suggest that PARP cleavage may occur as an independent event that can be disassociated with cell apoptosis. SN - 1357-2725 UR - https://www.unboundmedicine.com/medline/citation/14643888/Caspase_dependent_apoptosis_and__independent_poly_ADP_ribose__polymerase_cleavage_induced_by_transforming_growth_factor_beta1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357272503002152 DB - PRIME DP - Unbound Medicine ER -