دورية أكاديمية

Human umbilical cord blood cells induce neuroprotective change in gene expression profile in neurons after ischemia through activation of Akt pathway.

التفاصيل البيبلوغرافية
العنوان: Human umbilical cord blood cells induce neuroprotective change in gene expression profile in neurons after ischemia through activation of Akt pathway.
المؤلفون: Shahaduzzaman MD; Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, FL, USA., Mehta V, Golden JE, Rowe DD, Green S, Tadinada R, Foran EA, Sanberg PR, Pennypacker KR, Willing AE
المصدر: Cell transplantation [Cell Transplant] 2015; Vol. 24 (4), pp. 721-35. Date of Electronic Publication: 2015 Feb 26.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: SAGE Publishing Country of Publication: United States NLM ID: 9208854 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-3892 (Electronic) Linking ISSN: 09636897 NLM ISO Abbreviation: Cell Transplant Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : Thousand Oaks, CA : SAGE Publishing
Original Publication: Elmsford, New York : Pergamon Press, c1992-
مواضيع طبية MeSH: Gene Expression Regulation* , Transcriptome*, Fetal Blood/*metabolism , Infarction, Middle Cerebral Artery/*pathology , Neurons/*metabolism , Proto-Oncogene Proteins c-akt/*metabolism, Animals ; Binding Sites ; Cells, Cultured ; Coculture Techniques ; Fetal Blood/cytology ; Fetal Blood/transplantation ; Humans ; Immunohistochemistry ; Infarction, Middle Cerebral Artery/metabolism ; Infarction, Middle Cerebral Artery/therapy ; Neurons/cytology ; Neuroprotective Agents ; Oligonucleotide Array Sequence Analysis ; Peroxiredoxins/genetics ; Peroxiredoxins/metabolism ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transcription Factors/chemistry ; Transcription Factors/metabolism
مستخلص: Human umbilical cord blood (HUCB) cell therapies have shown promising results in reducing brain infarct volume and most importantly in improving neurobehavioral function in rat permanent middle cerebral artery occlusion, a model of stroke. In this study, we examined the gene expression profile in neurons subjected to oxygen-glucose deprivation (OGD) with or without HUCB treatment and identified signaling pathways (Akt/MAPK) important in eliciting HUCB-mediated neuroprotective responses. Gene chip microarray analysis was performed using RNA samples extracted from the neuronal cell cultures from four experimental groups: normoxia, normoxia+HUCB, OGD, and OGD+HUCB. Both quantitative RT-PCR and immunohistochemistry were carried out to verify the microarray results. Using the Genomatix software program, promoter regions of selected genes were compared to reveal common transcription factor-binding sites and, subsequently, signal transduction pathways. Under OGD condition, HUCB cells significantly reduced neuronal loss from 68% to 44% [one-way ANOVA, F(3, 16)=11, p=0.0003]. Microarray analysis identified mRNA expression of Prdx5, Vcam1, CCL20, Alcam, and Pax6 as being significantly altered by HUCB cell treatment. Inhibition of the Akt pathway significantly abolished the neuroprotective effect of HUCB cells [one-way ANOVA, F(3, 11)=8.663, p=0.0031]. Our observations show that HUCB neuroprotection is dependent on the activation of the Akt signaling pathway that increases transcription of the Prdx5 gene. We concluded that HUCB cell therapy would be a promising treatment for stroke and other forms of brain injury by modifying acute gene expression to promote neural cell protection.
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معلومات مُعتمدة: R01 NS052839 United States NS NINDS NIH HHS; R01NS52839 United States NS NINDS NIH HHS
المشرفين على المادة: 0 (Neuroprotective Agents)
0 (Transcription Factors)
EC 1.11.1.15 (Peroxiredoxins)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
تواريخ الأحداث: Date Created: 20141122 Date Completed: 20151231 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4739737
DOI: 10.3727/096368914X685311
PMID: 25413246
قاعدة البيانات: MEDLINE
الوصف
تدمد:1555-3892
DOI:10.3727/096368914X685311