| Item type: | Article | ||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | The Journal of biological chemistry | ||||||||||||||||||||||||||||||||
| Publisher: | American Society for Biochemistry and Molecular Biology | ||||||||||||||||||||||||||||||||
| Volume: | 286 | ||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 10 | ||||||||||||||||||||||||||||||||
| Page Range: | pp. 8030-8042 | ||||||||||||||||||||||||||||||||
| Date: | March 2011 | ||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) | ||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Dewey Decimal Classification: | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Partially | ||||||||||||||||||||||||||||||||
| Item ID: | 30613 |
Abstract
Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian ...
Abstract
Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1(-/-)-deficient mice. In the caput epididymis of Ido1(-/-) animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.
Metadata last modified: 25 May 2018 13:15
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