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Role of BNIP3 in TN...
Role of BNIP3 in TNF-induced cell death - TNF upregulates BNIP3 expression
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Ghavami, Saeid (författare)
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Eshraghi, Mehdi (författare)
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Kadkhoda, Kamran (författare)
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visa fler...
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Mutawe, Mark M. (författare)
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Maddika, Subbareddy (författare)
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Bay, Graham H. (författare)
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Wesselborg, Sebastian (författare)
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Halayko, Andrew J. (författare)
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Klonisch, Thomas (författare)
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Los, Marek Jan (författare)
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- Elsevier 2009
- 2009
- Engelska.
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889. ; 1793:3, 546-560
Abstract
Ämnesord
Stäng
- Tumor necrosis factor alpha (TNF) is a cytokine that induces caspase-dependent (apoptotic) and caspase-independent (necrosis-like) cell death in different cells. We used the murine fibrosarcoma cell line model L929 and a stable L929 transfectant over-expressing a mutated dominant-negative form of BNIP3 lacking the C-terminal transmembrane (TM) domain (L929-ΔTM-BNIP3) to test if TNF-induced cell death involved pro-apoptotic Bcl2 protein BNIP3. Treatment of cells with TNF in the absence of actinomycin D caused a rapid fall in the mitochondrial membrane potential (Δ Ψ m ) and a prompt increase in reactive oxygen species (ROS) production, which was significantly less pronounced in L929-ΔTM-BNIP3. TNF did not cause the mitochondrial release of apoptosis inducing factor (AIF) and Endonuclease G (Endo-G) but provoked the release of cytochrome c , Smac/Diablo, and Omi/HtrA2 at similar levels in both L929 and in L929-ΔTM-BNIP3 cells. We observed TNF-associated increase in the expression of BNIP3 in L929 that was mediated by nitric oxide and significantly inhibited by nitric oxide synthase inhibitor N 5 -(methylamidino)-l-ornithine acetate. In L929, lysosomal swelling and activation were markedly increased as compared to L929-ΔTM-BNIP3 and could be inhibited by treatment with inhibitors to vacuolar H + -ATPase and cathepsins −B/−L. Together, these data indicate that TNF-induced cell death involves BNIP3, ROS production, and activation of the lysosomal death pathway.
Ämnesord
- Natural Sciences (hsv)
- Biological Sciences (hsv)
- Biochemistry and Molecular Biology (hsv)
- Naturvetenskap (hsv)
- Biologiska vetenskaper (hsv)
- Biokemi och molekylärbiologi (hsv)
- Cell Biology (hsv)
- Cellbiologi (hsv)
Nyckelord
- Caspase; Cathepsin; Flow cytometry; Lysosome; ROS
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Till lärosätets databas
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Ghavami, Saeid
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Eshraghi, Mehdi
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Kadkhoda, Kamran
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Mutawe, Mark M.
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Maddika, Subbare ...
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Bay, Graham H.
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visa fler...
-
Wesselborg, Seba ...
-
Halayko, Andrew ...
-
Klonisch, Thomas
-
Los, Marek Jan
-
visa färre...
- Av lärosätet
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