NF-κB plays a key role in hypoxia-inducible factor-1–regulated erythropoietin gene expression

Figueroa, Yanira G.; Chan, Alex W.H.; Ibrahim, Rania; Tang, Yan; Burow, Matthew E.; Alam, Jawed; Scandurro, Aline B.; Beckman, Barbara S.

doi:10.1016/s0301-472x(02)00934-7

Cited by 78 publications

(62 citation statements)

References 41 publications

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“…Selective inhibition of nuclear factor (NF)-kB also results in significant decreases in HIF-1a and EPO expression during hypoxia (Figueroa et al, 2002). Interactions between these two important transcription factors have been proposed, although the mechanisms underpinning these interactions remain to be defined.…”

Section: Resultsmentioning

confidence: 99%

YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia

et al. 2007

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Section: Resultsmentioning

confidence: 99%

YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia

et al. 2007

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“…However, the mechanism for the change in HIF-1a concentration is undefined. It is noteworthy that YC-1 inhibited the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells (25), and that NF-nB plays a key role in HIF-1-regulated erythropoietin gene expression in the same cells has been reported (26). Activation of an NF-nB-dependent pathway in normoxic cells has been shown to stabilize HIF-1a (27).…”

Section: Discussionmentioning

confidence: 97%

YC-1 suppresses constitutive nuclear factor-κB activation and induces apoptosis in human prostate cancer cells

Huang

Pan

Guh

et al. 2005

Molecular Cancer Therapeutics

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Although the indazole compound, YC-1, is reported to exert anticancer activities in several cancer cell types, its target and mechanism of action have not been well explored. The objectives of this study were to ascertain whether YC-1 directly induces apoptosis in prostate cancer cells and to explore the mechanism(s) whereby YC-1 causes cell death. Hormone-refractory metastatic human prostate cancer PC-3 cells were selected for this study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay indicated that YC-1 suppresses growth of PC-3 cells in a concentration-dependent and timedependent manner. Apoptosis was determined using 4V,6-diamidino-2-phenylindole staining, and cell cycle progression was examined by FACScan flow cytometry. YC-1 treatment showed chromatin condensation and increased the percentage of PC-3 cells in the hypodiploid sub-G 0 -G 1 phase, indicative of apoptosis. Additionally, exposure to YC-1 was found to induce activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. Translocation and activation of nuclear factor-KB (NF-KB) were determined by immunofluorescent staining and ELISA, respectively. The results showed that YC-1 abolished constitutive nuclear translocation and activation of NF-KB/p65. Furthermore, inhibition of inhibitor of KBA (IKBA) phosphorylation and accumulation of IKBA were observed. The antitumor effects of YC-1 were evaluated by measuring the growth of tumor xenografts in YC-1-treated severe combined immunodeficient mice. The volumes of PC-3 tumors produced in severe combined immunodeficient mice were observed to decline significantly after treatment with YC-1 compared with vehicle controls. We concluded that the antitumor effects of YC-1 in PC-3 cells include the induction of apoptosis and the suppression of NF-KB activation. Given these unique actions, further investigations of the effects of YC-1 against hormone-refractory prostate cancer are warranted.

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“…Several studies suggest that the EPO neuroprotective signaling pathways have some similarities to the pathways in erythropoiesis, including activations of Janus-tyrosine kinase 2 (Jak2) (Bittorf et al, 1997;Kawakami et al, 2001), signal transducers and activators of transcription (STATs) (Bittorf et al, 2000;Damen et al, 1995) and of nuclear factor kappaB (NFkB) (Figueroa et al, 2002;Matsushita et al, 2003). When the EPO molecule binds to the EPOR, a dimerization of the receptor occurs with subsequent autophosphorylation of Jak2 and receptor activation.…”

Section: Discussionmentioning

confidence: 99%

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

Montero

Poulsen

Noraberg

et al. 2007

Experimental Neurology

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In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-D-aspartate (NMDA) excitotoxicity. Hippocampal slice cultures were pretreated for 24 h with 100 IU/ml EPO (= 26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49 ± 3 or 35 ± 8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33 ± 5 and 15 ± 8%, respectively, in the OGD and NMDA exposed cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of α-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least as efficient neuroprotectant as EPO when excitotoxicity is modeled in mouse hippocampal slice cultures.

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NF-κB plays a key role in hypoxia-inducible factor-1–regulated erythropoietin gene expression

Cited by 78 publications

References 41 publications

YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia

YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia

YC-1 suppresses constitutive nuclear factor-κB activation and induces apoptosis in human prostate cancer cells

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

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