Indoleamine 2,3-dioxygenase participates in the interferon-gamma-induced cell death process in cultured bovine luteal cells.
Indoleamine 2,3-dioxygenase participates in the interferon-gamma-induced cell death process in cultured bovine luteal cells.
复制标题
吲哚胺 2,3-双加氧酶参与培养的牛黄体细胞中干扰素 γ 诱导的细胞死亡过程。
DOI：
10.1095/biolreprod.105.042333
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发表时间：
2006
影响因子：
3.6
通讯作者：
Pate,JoyL
中科院分区：
文献类型：
--
作者：
Cannon,MatthewJ;Pate,JoyL
Interferon-gamma (IFNG) induces apoptotic cell death in bovine luteal cells, but the pathway(s) involved in this process are not well defined. Evidence supporting the involvement of an IFNG-inducible enzymatic pathway that degrades tryptophan in IFNG-induced death of bovine luteal cells is presented in this study. The IFNG-inducible enzyme indoleamine 2,3-dioxygenase (INDO) catalyzes the first step in a metabolic pathway that degrades tryptophan. In the first experiment, RT-PCR revealed the presence ofINDOmRNA in luteal cells treated with IFNG, but not in untreated cells. To determine whether INDO participates in IFNG-induced death of bovine luteal cells, an experiment was performed to test the effect of 1-methyl-d-tryptophan (1-MT), an inhibitor of INDO, on IFNG-induced DNA fragmentation in luteal cells. Single-cell gel electrophoresis and microscopic image analysis revealed that 1-MT inhibited DNA fragmentation induced by IFNG. To determine whether supplementation of cell cultures with additional tryptophan could also protect luteal cells from IFNG-induced DNA fragmentation, luteal cells were cultured in the presence of IFNG, andl-tryptophan was added to cultures to achieve final concentrations that were 5-, 10-, or 25-fold higher than the concentration ofl-tryptophan found in nonsupplemented culture medium. Supplementation of IFNG-treated luteal cell cultures with elevated concentrations of tryptophan also prevented IFNG-induced DNA fragmentation. We conclude that INDO participates in IFNG-induced death of bovine luteal cells, through a mechanism that involves degradation of tryptophan, thereby reducing tryptophan concentrations to a point insufficient to meet luteal cells needs.
