Tags

Type your tag names separated by a space and hit enter

Evidence for the involvement of Par-4 in ischemic neuron cell death.
J Cereb Blood Flow Metab. 2001 Apr; 21(4):334-43.JC

Abstract

After a stroke many neurons in the ischemic brain tissue die by a process called apoptosis, a form of cell death that may be preventable. The specific molecular cascades that mediate ischemic neuronal death are not well understood. The authors recently identified prostate apoptosis response-4 (Par-4) as a protein that participates in the death of cultured hippocampal neurons induced by trophic factor withdrawal and exposure to glutamate. Here, the authors show that Par-4 levels increase in vulnerable populations of hippocampal and striatal neurons in rats after transient forebrain ischemia; Par-4 levels increased within 6 hours of reperfusion and remained elevated in neurons undergoing apoptosis 3 days later. After transient focal ischemia in mice, Par-4 levels were increased 6 to 12 hours after reperfusion in the infarcted cortex and the striatum, and activation of caspase-8 occurred with a similar time course. Par-4 immunoreactivity was localized predominantly in cortical neurons at the border of the infarct area. A Par-4 antisense oligonucleotide protected cultured hippocampal neurons against apoptosis induced by chemical hypoxia and significantly reduced focal ischemic damage in mice. The current data suggest that early up-regulation of Par-4 plays a pivotal role in ischemic neuronal death in animal models of stroke and cardiac arrest.

Authors+Show Affiliations

Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11323519

Citation

Culmsee, C, et al. "Evidence for the Involvement of Par-4 in Ischemic Neuron Cell Death." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 21, no. 4, 2001, pp. 334-43.
Culmsee C, Zhu Y, Krieglstein J, et al. Evidence for the involvement of Par-4 in ischemic neuron cell death. J Cereb Blood Flow Metab. 2001;21(4):334-43.
Culmsee, C., Zhu, Y., Krieglstein, J., & Mattson, M. P. (2001). Evidence for the involvement of Par-4 in ischemic neuron cell death. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 21(4), 334-43.
Culmsee C, et al. Evidence for the Involvement of Par-4 in Ischemic Neuron Cell Death. J Cereb Blood Flow Metab. 2001;21(4):334-43. PubMed PMID: 11323519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for the involvement of Par-4 in ischemic neuron cell death. AU - Culmsee,C, AU - Zhu,Y, AU - Krieglstein,J, AU - Mattson,M P, PY - 2001/4/27/pubmed PY - 2001/5/18/medline PY - 2001/4/27/entrez SP - 334 EP - 43 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 21 IS - 4 N2 - After a stroke many neurons in the ischemic brain tissue die by a process called apoptosis, a form of cell death that may be preventable. The specific molecular cascades that mediate ischemic neuronal death are not well understood. The authors recently identified prostate apoptosis response-4 (Par-4) as a protein that participates in the death of cultured hippocampal neurons induced by trophic factor withdrawal and exposure to glutamate. Here, the authors show that Par-4 levels increase in vulnerable populations of hippocampal and striatal neurons in rats after transient forebrain ischemia; Par-4 levels increased within 6 hours of reperfusion and remained elevated in neurons undergoing apoptosis 3 days later. After transient focal ischemia in mice, Par-4 levels were increased 6 to 12 hours after reperfusion in the infarcted cortex and the striatum, and activation of caspase-8 occurred with a similar time course. Par-4 immunoreactivity was localized predominantly in cortical neurons at the border of the infarct area. A Par-4 antisense oligonucleotide protected cultured hippocampal neurons against apoptosis induced by chemical hypoxia and significantly reduced focal ischemic damage in mice. The current data suggest that early up-regulation of Par-4 plays a pivotal role in ischemic neuronal death in animal models of stroke and cardiac arrest. SN - 0271-678X UR - https://www.unboundmedicine.com/medline/citation/11323519/Evidence_for_the_involvement_of_Par_4_in_ischemic_neuron_cell_death_ DB - PRIME DP - Unbound Medicine ER -