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Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex.
J Neurochem. 2005 Apr; 93(1):26-37.JN

Abstract

Perinatal hypoxia/ischemia (HI) is a common cause of neurological deficits in children. Interleukin-1 (IL-1) activity has been implicated in HI-induced brain damage. However, the mechanisms underlying its action in HI have not been characterized. We used a 7-day-old rat model to elucidate the role of nuclear factor-kappaB (NF-kappaB) activation in HI stimulation of IL-1 signaling. HI was induced by permanent ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O(2)). Using ELISA assays, we observed increased cell death and caspase 3 activity in hippocampus and cortex 3, 6, 12, 24 and 48 h post-HI. IL-1beta protein expression increased, beginning at 3 h after HI and lasting until 24 h post-HI in hippocampus and 12 h post-HI in cortex. Intracerebroventricular injection of 2 microg IL-1 receptor antagonist (IL-1Ra) 2 h after HI significantly reduced cell death and caspase 3 activity. Electrophoretic mobility shift assay analyses of hippocampus and cortex after HI for NF-kappaB activity showed increased p65/p50 DNA-binding activity at 24 h post-HI. Western blot analyses showed significant nuclear translocation of p65. Protein expression levels of two known inflammatory agents, inducible nitric oxide synthase and cycloxygenase 2, known to be transcriptionally regulated by NF-kappaB, also increased at 24 h after HI. All these HI-induced changes were reversed by IL-1Ra blockade of IL-1 signaling, consistent with IL-1 triggering of inflammatory apoptotic outcomes via NF-kappaB transcriptional activation. The observed increase in cytoplasmic phosphorylated inhibitor kappaBalpha (IkappaBalpha) and nuclear translocation of Bcl-3 24 h after HI was also significantly attenuated by IL-1Ra blockade, suggesting that HI-induced IL-1 activation of NF-kappaB is via both the degradation of IkappaBalpha and the nuclear translocation of Bcl-3.

Authors+Show Affiliations

Department of Anatomy and Neuroscience, University of Texas Medical Branch, Galveston, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15773902

Citation

Hu, Xiaoming, et al. "Activation of Nuclear factor-kappaB Signaling Pathway By Interleukin-1 After Hypoxia/ischemia in Neonatal Rat Hippocampus and Cortex." Journal of Neurochemistry, vol. 93, no. 1, 2005, pp. 26-37.
Hu X, Nesic-Taylor O, Qiu J, et al. Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. J Neurochem. 2005;93(1):26-37.
Hu, X., Nesic-Taylor, O., Qiu, J., Rea, H. C., Fabian, R., Rassin, D. K., & Perez-Polo, J. R. (2005). Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. Journal of Neurochemistry, 93(1), 26-37.
Hu X, et al. Activation of Nuclear factor-kappaB Signaling Pathway By Interleukin-1 After Hypoxia/ischemia in Neonatal Rat Hippocampus and Cortex. J Neurochem. 2005;93(1):26-37. PubMed PMID: 15773902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. AU - Hu,Xiaoming, AU - Nesic-Taylor,Olivera, AU - Qiu,Jingxin, AU - Rea,Harriett C, AU - Fabian,Roderick, AU - Rassin,David K, AU - Perez-Polo,J Regino, PY - 2005/3/19/pubmed PY - 2005/5/17/medline PY - 2005/3/19/entrez SP - 26 EP - 37 JF - Journal of neurochemistry JO - J Neurochem VL - 93 IS - 1 N2 - Perinatal hypoxia/ischemia (HI) is a common cause of neurological deficits in children. Interleukin-1 (IL-1) activity has been implicated in HI-induced brain damage. However, the mechanisms underlying its action in HI have not been characterized. We used a 7-day-old rat model to elucidate the role of nuclear factor-kappaB (NF-kappaB) activation in HI stimulation of IL-1 signaling. HI was induced by permanent ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O(2)). Using ELISA assays, we observed increased cell death and caspase 3 activity in hippocampus and cortex 3, 6, 12, 24 and 48 h post-HI. IL-1beta protein expression increased, beginning at 3 h after HI and lasting until 24 h post-HI in hippocampus and 12 h post-HI in cortex. Intracerebroventricular injection of 2 microg IL-1 receptor antagonist (IL-1Ra) 2 h after HI significantly reduced cell death and caspase 3 activity. Electrophoretic mobility shift assay analyses of hippocampus and cortex after HI for NF-kappaB activity showed increased p65/p50 DNA-binding activity at 24 h post-HI. Western blot analyses showed significant nuclear translocation of p65. Protein expression levels of two known inflammatory agents, inducible nitric oxide synthase and cycloxygenase 2, known to be transcriptionally regulated by NF-kappaB, also increased at 24 h after HI. All these HI-induced changes were reversed by IL-1Ra blockade of IL-1 signaling, consistent with IL-1 triggering of inflammatory apoptotic outcomes via NF-kappaB transcriptional activation. The observed increase in cytoplasmic phosphorylated inhibitor kappaBalpha (IkappaBalpha) and nuclear translocation of Bcl-3 24 h after HI was also significantly attenuated by IL-1Ra blockade, suggesting that HI-induced IL-1 activation of NF-kappaB is via both the degradation of IkappaBalpha and the nuclear translocation of Bcl-3. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15773902/Activation_of_nuclear_factor_kappaB_signaling_pathway_by_interleukin_1_after_hypoxia/ischemia_in_neonatal_rat_hippocampus_and_cortex_ L2 - https://doi.org/10.1111/j.1471-4159.2004.02968.x DB - PRIME DP - Unbound Medicine ER -