Indoleamine 2,3-dioxygenase 1 (IDO1) catabolizes tryptophan to kynurenine at the first step of tryptophan metabolism. Recently, in addition to IDO1, a new isoform called IDO2 was identified. In this study, we examined the tissue expression pattern of IDO2 mRNA and the cellular localization of expressed IDO2 protein in mice. IDO1 mRNA expression was observed in the colon and epididymis, whereas IDO2 mRNA expression was found in the cerebral cortex, liver, kidney, and epididymis. Immunohistochemical analysis revealed that IDO2 protein was exclusively expressed on the hepatocytes, interlobular bile ducts, neuronal cells of the cerebrum cortex, Purkinje cells of the cerebellum cortex, lamina epithelialis, proximal convoluted tubule, and the collecting tubule of the kidney. In the epididymis, IDO1 protein expression was restricted to the caput, whereas IDO2 protein expression was observed on the caput, corpus, and cauda. Both IDO proteins were expressed on the caput, but both showed a different protein expression pattern in the segments. Immunohistochemical analysis in IDO1(-/-) mouse epididymis showed that IDO2 protein was extensively upregulated due to the loss of IDO1 expression.

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.