Induction of indoleamine 2, 3-dioxygenase by death receptor activation contributes to apoptosis of melanoma cells via mitochondrial damage-dependent ROS accumulation
Authors: Frank Essmann
Mohamed Hassan
Turgut Cetindere
Simeon Santourlidis
Sandeep Nambiar
Journal: Cellular Signalling (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Indoleamine 2, 3-dioxygenase (IDO); transcriptional regulation; apoptotic mediator; anti-Fas agonist antibody; TNF-alpha
Affiliations: Clinic of Dermatology, University Hospital of Duesseldorf, Germany.

Abstract:  Although the induction of indoleamine 2, 3-dioxygenase (IDO) by several agents is well established, the mechanisms of its transcriptional regulation and those regulating its function as apoptotic mediator seem to be complex, agent-dependent, and cell type-specific. Besides their pro-apoptotic activity in melanoma cells, both anti-Fas agonist antibody (CH11) and the tumor necrosis factor (TNF)-alpha were found to induce IDO gene expression, the activation of apoptosis signal-regulating kinase (ASK1), and the activation of both c-Jun N-terminal kinase (JNK) and NF-kappaB pathways. In addition, the treatment of melanoma cells with CH11 or TNF-alpha induced the loss of mitochondrial membrane potential (Deltapsim), the accumulation of reactive oxygen species (ROS), the phosphorylation of Fas-associated domain (FADD), the cleavage of caspase-8, and truncation of Bid. Using RNA interference and pharmacological inhibitors, we could confirm the pro-apoptotic activity of IDO and address the mechanisms, which are responsible for its transcriptional regulation and the modulation of its pro-apoptotic activity during death receptor activation in melanoma cells. Thus, our data confirm the pro-apoptotic activity of IDO and provide an insight into the molecular mechanism of TNF-alpha and CH11-induced IDO expression, and the mechanism whereby IDO induces apoptosis of melanoma cells. 

Retracted: No

PubPeer comments:
 May 2011 megacorrection, found here: https: www.sciencedirect.com science article pii S089865681100009X It reads:  The authors regret that there were errors in Fig. 1B, Fig. 2C, Fig. 3D, Fig. 3E of the above publication. The corrected versions of the figures are reproduced here. The corrections do not influence either the validity of the published data or the conclusions described in the article. We apologise for these mistakes. There is unfortunately not a lot of details on the errors in these figures. Here are the original figures with some potential concerns. * Figure 1B: Three panels were replaced. The problem here appears to be a duplication between two panels, marked by me here with red boxes. Note that the measured percentages were a bit different between the two duplicated panels, suggesting this might not have been a simple misplacement error. ![file] * Figure 2C: In this figure, the b-actin (bottom) panels were all replaced. The problem here appears to be overlapping bands between panels in the original Figure 2C, but there are also overlaps within Figure 1C and between Figure 1C and 2C that were NOT addressed in this correction. Marked by me with arrows of the same color. ![file] * Figure 3D. Here, all JNK panels were replaced. I noted an overlap between two of the panels in the original figure, which I marked here with pink arrows. ![file] * Figure 3E This panel was completely replaced, but it is not clear what the problem was. , 
 The b-actin bands from Figure 1C and 2C also look remarkably similar to b-Actin bands in Figure 1 from an older paper from the last author, i.e. Denis Selimovic and Mohamed Hassan, Bosnian Journal of Basic Medical Sciences 2008, DOI: 10.17305 bjbms.2008.2988 Here is Figure 1 from that 2008 paper, in mirror image: ![file] ,