Role of BNIP3 in TNF-induced cell death - TNF upregulates BNIP3 expression
2009 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, Vol. 1793, no 3, 546-560 p.Article in journal (Refereed) Published
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 (ΔΨm) 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 N5-(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.
Place, publisher, year, edition, pages
Elsevier, 2009. Vol. 1793, no 3, 546-560 p.
Caspase; Cathepsin; Flow cytometry; Lysosome; ROS
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:liu:diva-86912DOI: 10.1016/j.bbamcr.2009.01.002ISI: 000264271500012OAI: oai:DiVA.org:liu-86912DiVA: diva2:583131