Differential NF-κB regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia

Jingxin Qiu, Marjorie R. Grafe, Shannon M. Schmura, Joel N. Glasgow, Thomas A. Kent, David K. Rassin, J. Regino Perez-Polo

Research output: Contribution to journalArticle

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Abstract

Cell death often occurs after hypoxic/ischemic injury to the central nervous system. Changes in levels of the anti-apoptotic Bcl-XL protein may be a determining factor in hypoxia-induced neuronal apoptosis. The transcription factor NF-κB regulates bcl-x gene expression. In this study, we examined the role of NF-κB in the regulation of bcl-x in hypoxia-induced cell death. Rat hippocampus and basal forebrain tissues were collected at different time points after hypoxia (7%O2, 93% N2 for 10 or 20 min). We found that 1) hypoxia induced apoptosis in the hippocampus and basal forebrain; 2) the NF-κB dimers c-Rel/p50 and p50/p50 bound to the bcl-x promoter NF-κB sequence (CS4) in the hippocampus, but only p50/p50 bound to the CS4 sequence in the basal forebrain and hypoxia-induced differential binding patterns of c-Rel/p50 and p50/p50 correlated with the bcl-x expression pattern in the hippocampus; 3) the hypoxia-induced patterns of binding of c-Rel/p50 to the bcl-x promoter CS4 sequence were different from those to the IgG-κB enhancer sequence, whereas those of p50/p50 were similar to both sequences; 4) nuclear protein levels of c-Rel, but not p50, correlated with the c-Rel/p50 DNA binding patterns to the bcl-x CS4 site; and 5) there were differential responses to hypoxia among the different NF-κB protein subunits. These results suggest that there is a tissue-specific regulation of bcl-x gene expression by NF-κB in hypoxia-induced cell death in the hippocampus. The absence of these regulating features in the basal forebrain may account for the early appearance of apoptosis in response to hypoxia as compared with that in hippocampus.

Original languageEnglish (US)
Pages (from-to)223-234
Number of pages12
JournalJournal of Neuroscience Research
Volume64
Issue number3
DOIs
StatePublished - May 1 2001

Fingerprint

Hippocampus
Gene Expression
Cell Death
Apoptosis
bcl-X Protein
Basal Forebrain
Hypoxia
Apoptosis Regulatory Proteins
Protein Subunits
Nuclear Proteins
Transcription Factors
Central Nervous System
Immunoglobulin G
DNA
Wounds and Injuries

Keywords

  • Apoptosis
  • Bcl-x
  • c-Rel
  • Hypoxia
  • NF-κ
  • p50

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Qiu, J., Grafe, M. R., Schmura, S. M., Glasgow, J. N., Kent, T. A., Rassin, D. K., & Regino Perez-Polo, J. (2001). Differential NF-κB regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia. Journal of Neuroscience Research, 64(3), 223-234. https://doi.org/10.1002/jnr.1070

Differential NF-κB regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia. / Qiu, Jingxin; Grafe, Marjorie R.; Schmura, Shannon M.; Glasgow, Joel N.; Kent, Thomas A.; Rassin, David K.; Regino Perez-Polo, J.

In: Journal of Neuroscience Research, Vol. 64, No. 3, 01.05.2001, p. 223-234.

Research output: Contribution to journalArticle

Qiu, J, Grafe, MR, Schmura, SM, Glasgow, JN, Kent, TA, Rassin, DK & Regino Perez-Polo, J 2001, 'Differential NF-κB regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia', Journal of Neuroscience Research, vol. 64, no. 3, pp. 223-234. https://doi.org/10.1002/jnr.1070
Qiu, Jingxin ; Grafe, Marjorie R. ; Schmura, Shannon M. ; Glasgow, Joel N. ; Kent, Thomas A. ; Rassin, David K. ; Regino Perez-Polo, J. / Differential NF-κB regulation of bcl-x gene expression in hippocampus and basal forebrain in response to hypoxia. In: Journal of Neuroscience Research. 2001 ; Vol. 64, No. 3. pp. 223-234.
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