Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor
BackgroundCognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more n...
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Korean Diabetes Association
2016-09-01
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Series: | Diabetes & Metabolism Journal |
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Online Access: | https://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-40-396.pdf |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Na Han You Jeong Kim Su Min Park Seung Man Kim Ji Suk Lee Hye Sook Jung Eun Ju Lee Tae Kyoon Kim Tae Nyun Kim Min Jeong Kwon Soon Hee Lee Mi-kyung Kim Byoung Doo Rhee Jeong Hyun Park |
spellingShingle |
Na Han You Jeong Kim Su Min Park Seung Man Kim Ji Suk Lee Hye Sook Jung Eun Ju Lee Tae Kyoon Kim Tae Nyun Kim Min Jeong Kwon Soon Hee Lee Mi-kyung Kim Byoung Doo Rhee Jeong Hyun Park Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor Diabetes & Metabolism Journal Apoptosis Forkhead box O PC-12 cell Phosphatidylinositol 3-kinase/Akt pathway Reperfusion |
author_facet |
Na Han You Jeong Kim Su Min Park Seung Man Kim Ji Suk Lee Hye Sook Jung Eun Ju Lee Tae Kyoon Kim Tae Nyun Kim Min Jeong Kwon Soon Hee Lee Mi-kyung Kim Byoung Doo Rhee Jeong Hyun Park |
author_sort |
Na Han |
title |
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor |
title_short |
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor |
title_full |
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor |
title_fullStr |
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor |
title_full_unstemmed |
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor |
title_sort |
repeated glucose deprivation/reperfusion induced pc-12 cell death through the involvement of foxo transcription factor |
publisher |
Korean Diabetes Association |
series |
Diabetes & Metabolism Journal |
issn |
2233-6079 2233-6087 |
publishDate |
2016-09-01 |
description |
BackgroundCognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion.MethodsPC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions.ResultsCompared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells.ConclusionRepeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis. |
topic |
Apoptosis Forkhead box O PC-12 cell Phosphatidylinositol 3-kinase/Akt pathway Reperfusion |
url |
https://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-40-396.pdf |
work_keys_str_mv |
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doaj-3b0a0035c9b14de9b59af21b753f0a702020-11-24T23:40:47ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872016-09-0140539640510.4093/dmj.2016.40.5.396Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription FactorNa Han0You Jeong Kim1Su Min Park2Seung Man Kim3Ji Suk Lee4Hye Sook Jung5Eun Ju Lee6Tae Kyoon Kim7Tae Nyun Kim8Min Jeong Kwon9Soon Hee Lee10Mi-kyung Kim11Byoung Doo Rhee12Jeong Hyun Park13Division of Endocrinology and Metabolism, Department of Internal Medicine, Onhospital, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.BackgroundCognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion.MethodsPC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions.ResultsCompared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells.ConclusionRepeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.https://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-40-396.pdfApoptosisForkhead box OPC-12 cellPhosphatidylinositol 3-kinase/Akt pathwayReperfusion |