TNFalpha protects tissue resident stem cells from H2O2 induced apoptosis through a novel NF-small ka, CyrillicB p50/p50 homodimer mediated signaling pathway.
The objective of our study was to determine whether TNFalpha can protect tissue resident stem cells from hydrogen peroxide (H(2)O(2)) induced apoptosis. Apoptosis was measured via fluorescence activated flow cytometry of fluorescein-conjugated Annexin V in passage 3 human ASCs. Our data show that application of 300muM H(2)O(2) for 3h induced a high number of cells to undergo apoptosis. The number of apoptotic cells significantly decreased when cells were preincubated with TNFalpha. TNFalpha caused a rapid activation of NF-kappaB within 15min as evidenced by gel shift assay (EMSA). On further dissection of the NF-small ka, CyrillicB complex, the p50 subunit which generally forms heterodimers with p65 appears to form a p50/p50 homodimer instead of conventional p50/p65 heterodimer. This novel finding has implications for tissue regeneration and might as well be of importance for cancer cell growth and tumor progression.
Droll
Lilly
L
Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, SCRB2, Box 951, 7435 Fannin Street, Houston, TX 77054, USA.
Song
Yao-Hua
YH
Krohn
Alexander
A
Muehlberg
Fabian
F
Alt
Eckhard
E
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D019610:Cytoprotection; D019281:Dimerization; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide