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Full-Text Articles in Medicine and Health Sciences
The Aryl Hydrocarbon Receptor Binds To E2f1 And Inhibits E2f1-Induced Apoptosis., Jennifer L Marlowe, Yunxia Fan, Xiaoqing Chang, Li Peng, Erik S Knudsen, Ying Xia, Alvaro Puga
The Aryl Hydrocarbon Receptor Binds To E2f1 And Inhibits E2f1-Induced Apoptosis., Jennifer L Marlowe, Yunxia Fan, Xiaoqing Chang, Li Peng, Erik S Knudsen, Ying Xia, Alvaro Puga
Kimmel Cancer Center Faculty Papers
Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr(-/-) fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, gammaH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of …
The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey
The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey
Dartmouth Scholarship
Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific …