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Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats.
Neurochem Int. 2006 Jun; 48(8):687-95.NI

Abstract

Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in cells. In this study, we reported an early, time-related, gradual up-regulation of HIF-1alpha, and a moderate increase in vascular endothelial growth factor (VEGF)- and erythropoietin (Epo)-levels following transient focal ischemia. Moreover, we demonstrated, for the first time a specific localization of the pro-apoptotic regulator BNIP3 in striatal and cortical neurons after transient focal ischemia in rats. Prolonged intranuclear BNIP3 immunoreactivity was associated with delayed neuronal death. Experiments showed protein increases on Western blots of brain tissue with peaks at 48h after ischemia. Epo responds to ischemia in an early stage, whereas VEGF and BNIP3 accumulate in cells at later times after ischemia. This suggests the possibility that BH3-only proteins might be one of the major downstream effectors of HIF-1alpha in hypoxic cell death. These findings open the possibility that the hypoxia-regulated pro-apoptotic protein BNIP3 enters the nucleus and could interact with other proteins involved in DNA structure, transcription or mRNA splicing after focal brain ischemia.

Authors+Show Affiliations

Institut für Molekulare und Zelluläre Anatomie, Universitätsklinikum, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16464515

Citation

Althaus, J, et al. "Expression of the Gene Encoding the Pro-apoptotic BNIP3 Protein and Stimulation of Hypoxia-inducible Factor-1alpha (HIF-1alpha) Protein Following Focal Cerebral Ischemia in Rats." Neurochemistry International, vol. 48, no. 8, 2006, pp. 687-95.
Althaus J, Bernaudin M, Petit E, et al. Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. Neurochem Int. 2006;48(8):687-95.
Althaus, J., Bernaudin, M., Petit, E., Toutain, J., Touzani, O., & Rami, A. (2006). Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. Neurochemistry International, 48(8), 687-95.
Althaus J, et al. Expression of the Gene Encoding the Pro-apoptotic BNIP3 Protein and Stimulation of Hypoxia-inducible Factor-1alpha (HIF-1alpha) Protein Following Focal Cerebral Ischemia in Rats. Neurochem Int. 2006;48(8):687-95. PubMed PMID: 16464515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. AU - Althaus,J, AU - Bernaudin,M, AU - Petit,E, AU - Toutain,J, AU - Touzani,O, AU - Rami,A, Y1 - 2006/02/07/ PY - 2005/10/12/received PY - 2005/11/29/revised PY - 2005/12/06/accepted PY - 2006/2/9/pubmed PY - 2006/7/26/medline PY - 2006/2/9/entrez SP - 687 EP - 95 JF - Neurochemistry international JO - Neurochem Int VL - 48 IS - 8 N2 - Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in cells. In this study, we reported an early, time-related, gradual up-regulation of HIF-1alpha, and a moderate increase in vascular endothelial growth factor (VEGF)- and erythropoietin (Epo)-levels following transient focal ischemia. Moreover, we demonstrated, for the first time a specific localization of the pro-apoptotic regulator BNIP3 in striatal and cortical neurons after transient focal ischemia in rats. Prolonged intranuclear BNIP3 immunoreactivity was associated with delayed neuronal death. Experiments showed protein increases on Western blots of brain tissue with peaks at 48h after ischemia. Epo responds to ischemia in an early stage, whereas VEGF and BNIP3 accumulate in cells at later times after ischemia. This suggests the possibility that BH3-only proteins might be one of the major downstream effectors of HIF-1alpha in hypoxic cell death. These findings open the possibility that the hypoxia-regulated pro-apoptotic protein BNIP3 enters the nucleus and could interact with other proteins involved in DNA structure, transcription or mRNA splicing after focal brain ischemia. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/16464515/Expression_of_the_gene_encoding_the_pro_apoptotic_BNIP3_protein_and_stimulation_of_hypoxia_inducible_factor_1alpha__HIF_1alpha__protein_following_focal_cerebral_ischemia_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(06)00003-9 DB - PRIME DP - Unbound Medicine ER -