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Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus.

Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Research Abstract Details 

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  • Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Abstract Text:

    yongjun wangYongjun Wang,rajat singhRajat Singh,ashish c masseyAshish C Massey,saul s kaneSaul S Kane,susmita kaushikSusmita Kaushik,taneisha grantTaneisha Grant,youqing xiangYouqing Xiang,ana maria cuervoAna Maria Cuervo,mark j czajaMark J Czaja,

    Macroautophagy has been implicated as a mechanism of cell death. However, the relationship between this degradative pathway and cell death is unclear as macroautophagy has been shown recently to protect against apoptosis. To better define the interplay between these two critical cellular processes, we determined whether inhibition of macroautophagy could have both pro-apoptotic and anti-apoptotic effects in the same cell. Embryonic fibroblasts from mice with a knock-out of the essential macroautophagy gene atg5 were treated with activators of the extrinsic and intrinsic death pathways. Loss of macroautophagy sensitized these cells to caspase-dependent apoptosis from the death receptor ligands Fas and tumor necrosis factor-alpha (TNF-alpha). Atg5(-/-) mouse embryonic fibroblasts had increased activation of the mitochondrial death pathway in response to Fas/TNF-alpha in concert with decreased ATP levels. Fas/TNF-alpha treatment failed to up-regulate macroautophagy, and in fact, decreased activity at late time points. In contrast to their sensitization to Fas/TNF-alpha, Atg5(-/-) cells were resistant to death from menadione and UV light. In the absence of macroautophagy, an up-regulation of chaperone-mediated autophagy induced resistance to these stressors. These results demonstrate that inhibition of macroautophagy can promote or prevent apoptosis in the same cell and that the response is governed by the nature of the death stimulus and compensatory changes in other forms of autophagy. Experimental findings that an inhibition of macroautophagy blocks apoptosis do not prove that autophagy mediates cell death as this effect may result from the protective up-regulation of other autophagic pathways such as chaperone-mediated autophagy.

    Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Publishing Authors By Initials

    y wangY Wang,r singhR Singh,ac masseyAC Massey,ss kaneSS Kane,s kaushikS Kaushik,t grantT Grant,y xiangY Xiang,am cuervoAM Cuervo,mj czajaMJ Czaja,

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    Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 283

    Page Numbers: 4766-77

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 11

    MONTH: 12

    YEAR: 2007

    Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

    Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. Keywords Mesh Terms:

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    Grant and Affiliation Information for Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus.

    AFFILIATION: Departments of Medicine and Anatomy and Structural Biology.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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