Insulin-like growth factor-I-forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor-α-mediated neuronal damage: implications for human immunodeficiency virus encephalitis.
Insulin-like growth factor-I-forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor-α-mediated neuronal damage: implications for human immunodeficiency virus encephalitis.
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DOI：
10.1002/jnr.22542
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发表时间：
2011-02
影响因子：
4.2
通讯作者：
Reiss, Krzysztof
中科院分区：
文献类型：
--
作者：
Wilk, Anna;Urbanska, Katarzyna;Yang, Shuo;Wang, Jin Ying;Amini, Shohreh;Del Valle, Luis;Peruzzi, Francesca;Meggs, Leonard;Reiss, Krzysztof
In HIV patients, antiretroviral medications trigger metabolic abnormalities, including insulin resistance. In addition, the inflammatory cytokine tumor necrosis factor-α (TNFα), which is elevated in human immunodeficiency virus encephalitis (HIVE), also induces insulin resistance and inflicts neuronal damage in vitro. In differentiated PC12 cells and rat cortical neurons, high glucose (HG; 25 mM) triggers reactive oxygen species (ROS) accumulation, contributing to the retraction of neuronal processes, with only a minimal involvement of neuronal apoptosis. In the presence of TNFα, HG-treated neurons undergo massive apoptosis. Because mammalian homolog of the Forkhead family of transcription factors, Forkhead box O transcription factor 3a (FOXO3a), controls ROS metabolism, we asked whether FOXO3a could affect the fate of differentiated neurons in the paradigm of HIVE. We observed FOXO3a nuclear translocation in HG-treated neuronal cultures, accompanied by partial loss of mitochondrial potential and gradual retraction of neuronal processes. Addition of TNFα to HG-treated neurons increased expression of the FOXO-dependent proapoptotic gene Bim, which resulted in extensive apoptotic death. Insulin-like growth factor-I (IGF-I) significantly lowered intracellular ROS, which was accompanied by IGF-I-mediated FOXO3a nuclear export and decrease in its transcriptional activity. The clinical relevance of these findings is supported by detection of nuclear FOXO3a in TUNEL-positive cortical neurons from HIVE, especially in brain areas characterized by elevated TNFα.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1152/ajprenal.00215.2006
发表时间：
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