Focal ischemia induces expression of the DNA damage-inducible gene GADD45 in the rat brain

Jin, Ketao; Chen, J; Kawaguchi, Kenji; Rl, Zhu; Ra, Stetler; Rp, Simon; Sh, Graham

doi:10.1097/00001756-199607290-00022

Cited by 57 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The common carotid arteries (CCAs) were then exposed and ligated with microvascular clips for 15 min with continuous monitoring of the EEG. Sham-operated rats underwent identical surgical procedures, except that the CCAs were not ligated.Temporary focal ischemia of 20 or 90 min duration was induced using the suture occlusion technique, as described elsewhere (Jin et al, 1996), with modification. Male SpragueDawley rats (280 -310 g) were ventilated with 1.5% isoflurane in…”

mentioning

confidence: 99%

Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury

Jin¹,

Li²,

Nagayama³

et al. 2000

J. Neurosci. Res.

Self Cite

View full text Add to dashboard Cite

T-cell restricted intracellular antigen-related protein (TIAR) is an RNA recognition motif-type RNA-binding protein that has been implicated in the apoptotic death of T-lymphocytes and retinal pigment epithelial cells. Western blots prepared with a monoclonal antibody against TIAR showed expression in normal rat hippocampus, and induction by 15 min of global cerebral ischemia. This increased expression was evident at 8 hr after ischemia and maximal at 24 hr, whereas expression at 72 hr was reduced below basal levels. Expression of TIAR protein was also increased in parietal cortex 6 and 24 hr after 90 min of focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion, as well as in cultured cortical neurons and astroglia after exposure to hypoxia in vitro. Immunocytochemistry showed that increased expression of TIAR occurred mainly in the CA1 sector of hippocampus 24 hr after global ischemia, and in cortical and striatal neurons 24 hr after 20 or 90 min of focal ischemia. Double-labeling studies showed that TIAR protein expression was co-localized with DNA damage in neuronal cells. The findings suggest that TIAR may be involved in neuronal cell death after cerebral ischemic injury.

show abstract

mentioning

confidence: 99%

Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury

Jin¹,

Li²,

Nagayama³

et al. 2000

J. Neurosci. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some of the disparity between these smdies could be attributed to differences in how much of the core or adjacent surviving brain was sampled, because protein levels in the core for most genes would decrease. Also of interest is that at least one study shows induction of GADD45, growth arrest and DNA damage-inducible in neurons throughout an ischemic hemisphere, in areas inside and outside any region of ischemia (Jin et al, 1996). This pattern of gene induction is similar to that of immediate early genes (lEGs) described below; hence, it is likely induced in response to spreading depression rather than damaged DNA (though once induced it could respond to DNA damage after focal ischemia).…”

Section: Apoptosis Dna Damaging Induciblementioning

confidence: 83%

Signal Transduction and Gene Regulation During Hypoxia Stress: A Potential Role in Neurodegenerative Disease

Millhorn¹

2002

View full text Add to dashboard Cite

Public reporting burden for this collection of infomiation is estimated to average 1 hour per response, including the time for reviewing instnjctions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway. Suite 1204, Arlington, VA 22202-4302, and PERFORMING ORGANIZATION NAIVIE(S) AND ADDRESS(ES)University of Cincinnati Cincinnati, Ohio 45267-0553 E-Mail: david.millhorn@uc.edu Soldiers deployed to high altitude terrain or exposed to chemical toxins that induce ischemia or impaired oxidative metabolism in the central nervous system (CNS) encounter sustained cellular hypoxia. This can compromise CNS function and lead to permanent neuronal injury, which is a precursor for neurodegenerative disorders such as Alzheimer's disease. The proposed research is designed to determine the role of stress-activated signal transduction systems in regulating a cellular phenotype that is tolerant to hypoxic stress. We hypothesize that de novo gene expression is a major component of the adaptative/protective response to hypoxia, and that the p38 kinase stress-activated pathway plays a major role in this response. We present novel preliminary findings, which show that genes involved in cell proliferation and differentiation are regulated by hypoxia and p38. We hypothesize that these genes and the genes that encode immediate early transcription factors, and the hypoxia-sensitive potassium channels are regulated by p38 during hypoxia and play a major role in protecting neurons form hypoxia injury and neurodegenerative disease. Studies are performed in PCI2 cells, which are extremely tolerant to reduced oxygen and a widely used model for elucidating the molecular mechanisms of neural function. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)UThe objectives of the proposed research are: 1) Identify the p38 isoforms that are activated by hypoxia. Determine the effects of hypoxia on the protein kinases and small G-proteins that lie upstream of p38. 2) Determine the role of the p38 kinase pathway on the unique hypoxia-induced regulation of cyclin A, and immediate early genes in thsfos and jun families. 3) Determine the role of the p38 kinase pathway in regulating the hypoxia-induced expression of the oxygen-sensitive Kvl.2 potassium channel.14. SUBJECT TERMS hypoxia, p38 kinase pathways, cyclin A, immediate early genes, potassium channels, signal transduction, pheochromocytoma cells, neurodegenerative disease References 10Appendices 10 IntroductionThe research in this project was undertaken to determine the role of stress-activated signal transduction systems in regulating a cellular phenotype that can survive and function during hypoxic stress. The general hypothesis is that reduced 02 c...

show abstract

“…Other members of this family are the alpha, beta, and gamma forms of the gene for growth arrest DNA damage-inducible protein (GADD45), which were all induced after HI. Some of them have previously been reported after ischemia in the immature (only GADD45 alpha) (Charriaut-Marlangue et al, 1999) and mature brain (Jin et al, 1996). Gadd45 alpha, beta, and gamma are induced by DNA damage and seem to serve similar, but not identical, functions along different apoptotic and growth inhibitory pathways.…”

Section: Genes Related To Apoptotic/cell Deathmentioning

confidence: 98%

Global Gene Expression in the Immature Brain after Hypoxia-Ischemia

Hedtjärn¹,

Mallard²,

Eklind

et al. 2004

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Summary:Ischemia induces a complex response of differentially expressed genes in the brain. In order to understand the specific mechanisms of injury in the developing brain, it is important to obtain information on global changes in the transcriptome after neonatal hypoxia-ischemia. In this study, oligonucleotide arrays were used to investigate genomic changes at 2, 8, 24, and 72 hours after neonatal hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia (10% O 2 ). In total, 343 genes were differentially expressed in cortex, hippocampus, thalamus, and striatum 2 to 72 hours after hypoxia-ischemia, when comparing ipsilateral with contralateral hemispheres and with controls, using the significance analysis for microarrays. A total of 283 genes were upregulated and 60 were downregulated, and 94% of the genes had not previously been shown after neonatal hypoxia-ischemia. Genes related to transcription factors and metabolism had mostly upregulated transcripts, whereas most downregulated genes belonged to the categories of ion and vesicular transport and signal transduction. Genes involved in transcription, stress, and apoptosis were induced early after the insult, and many new genes that may play important roles in the pathophysiology of neonatal hypoxiaischemia were identified.

show abstract

Focal ischemia induces expression of the DNA damage-inducible gene GADD45 in the rat brain

Cited by 57 publications

References 0 publications

Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury

Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury

Signal Transduction and Gene Regulation During Hypoxia Stress: A Potential Role in Neurodegenerative Disease

Global Gene Expression in the Immature Brain after Hypoxia-Ischemia

Contact Info

Product

Resources

About