Mitochondrial function and nuclear factor-kappaB-mediated signaling in radiation-induced bystander effects
Authors: Hongning Zhou
Yu-Chin Lien
Vladimir N Ivanov
Mercy Davidson
Tom K Hei
Journal: Cancer research (2008)
Discipline: CLINICAL MEDICINE
Keywords: radiation-induced bystander effects; signaling processes; mitochondrial DNA-depleted; human skin fibroblasts; Columbia University charged particle microbeam
Affiliations: Center for Radiological Research, College of Physicians and Surgeons, Mailman School of Public Health, Columbia University, New York, NY, USA.

Abstract:  Although radiation-induced bystander effects have been well described over the past decade, the mechanisms of the signaling processes involved in the bystander phenomenon remain unclear. In the present study, using the Columbia University charged particle microbeam, we found that mitochondrial DNA-depleted human skin fibroblasts (rho(o)) showed a higher bystander mutagenic response in confluent monolayers when a fraction of the same population were irradiated with lethal doses compared with their parental mitochondrial-functional cells (rho(+)). However, using mixed cultures of rho(o) and rho(+) cells and targeting only one population of cells with a lethal dose of alpha-particles, a decreased bystander mutagenesis was uniformly found in nonirradiated bystander cells of both cell types, indicating that signals from one cell type can modulate expression of bystander response in another cell type. In addition, we found that Bay 11-7082, a pharmacologic inhibitor of nuclear factor-kappaB (NF-kappaB) activation, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of nitric oxide (NO), significantly decreased the mutation frequency in both bystander rho(o) and rho(+) cells. Furthermore, we found that NF-kappaB activity and its dependent proteins, cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), were lower in bystander rho(o) cells when compared with their rho(+) counterparts. Our results indicated that mitochondria play an important role in the regulation of radiation-induced bystander effects and that mitochondria-dependent NF-kappaB/iNOS/NO and NF-kappaB/COX-2/prostaglandin E2 signaling pathways are important to the process. 

Retracted: No

PubPeer comments:
 Data in Exp Cell Res. 2011 Jul 1;317(11):1548-66 looks very similar to data in Cancer Res. 2008 Apr 1;68(7):2233-40 https: imgur.com cgWsAP4 https: pubpeer.com publications 7033E3CF59A77EB729AA5B21B8E31D#11 , 
 #1 We would like to thank Mr. Cortinarius Rufolatus for finding an error in our paper Exp Cell Res, 317 (11):1548-66, Figure 5B, where a wrong Western blot for PTGS2 (COX2) was used. We analyzed our data and found a step when this error in assembly of the figure occurred. We demonstrate in this comment the correct blot for PTGS2 (COX2) in the updated Figure 5B. Vertical lines in several blots indicate that some lanes (after additional treatment, which was not used in the paper) were removed. We would like to highlight that the correction was done for Exp. Cell Res paper, while Figure 4B in u201cCancer Resu201d paper (2008, 68:2233-224) is correct and contains solid data. ![file] ,