TNFα protects tissue resident stem cells from H2O2 induced apoptosis through a novel NF-κB p50/p50 homodimer mediated signaling pathway

The objective of our study was to determine whether TNF alpha can protect tissue resident stem cells from hydrogen peroxide (H2O2) 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 300 mu M H2O2 for 3 h induced a high number of cells to undergo apoptosis. The number of apoptotic cells significantly decreased when cells were preincubated with TNF alpha. TNF alpha caused a rapid activation of NF-kappa B within 15 min as evidenced by gel shift assay (EMSA). On further dissection of the NF-kappa B 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. (C) 2008 Elsevier Inc. All rights reserved.