Cited 81 times in
Role of Calcium in Pancreatic Islet Cell Death by IFN-γ/TNF-α1
DC Field | Value | Language |
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dc.contributor.author | 장인익 | - |
dc.date.accessioned | 2015-07-14T17:30:05Z | - |
dc.date.available | 2015-07-14T17:30:05Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/113009 | - |
dc.description.abstract | We studied the intracellular events associated with pancreatic β cell apoptosis by IFN-γ/TNF-α synergism. IFN-γ/TNF-α treatment of MIN6N8 insulinoma cells increased the amplitude of high voltage-activated Ca2+ currents, while treatment with IFN-γ or TNF-α alone did not. Cytosolic Ca2+ concentration ([Ca2+]c) was also increased by IFN-γ/TNF-α treatment. Blockade of L-type Ca2+ channel by nifedipine abrogated death of insulinoma cells by IFN-γ/TNF-α. Diazoxide that attenuates voltage-activated Ca2+ currents inhibited MIN6N8 cell death by IFN-γ/TNF-α, while glibenclamide that accentuates voltage-activated Ca2+ currents augmented insulinoma cell death. A protein kinase C inhibitor attenuated MIN6N8 cell death and the increase in [Ca2+]c by IFN-γ/TNF-α. Following the increase in [Ca2+]c, calpain was activated, and calpain inhibitors decreased insulinoma cell death by IFN-γ/TNF-α. As a downstream of calpain, calcineurin was activated and the inhibition of calcineurin activation by FK506 diminished insulinoma cell death by IFN-γ/TNF-α. BAD phosphorylation was decreased by IFN-γ/TNF-α because of the increased calcineurin activity, which was reversed by FK506. IFN-γ/TNF-α induced cytochrome c translocation from mitochondria to cytoplasm and activation of caspase-9. Effector caspases such as caspase-3 or -7 were also activated by IFN-γ/TNF-α treatment. These results indicate that IFN-γ/TNF-α synergism induces pancreatic β cell apoptosis by Ca2+ channel activation followed by downstream intracellular events such as mitochondrial events and caspase activation and also suggest the therapeutic potential of Ca2+ modulation in type 1 diabetes. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 7008~7014 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis* | - |
dc.subject.MESH | Calcineurin/physiology | - |
dc.subject.MESH | Calcium/physiology* | - |
dc.subject.MESH | Carrier Proteins/metabolism | - |
dc.subject.MESH | Caspases/metabolism | - |
dc.subject.MESH | Cytochromes c/metabolism | - |
dc.subject.MESH | Interferon-gamma/pharmacology* | - |
dc.subject.MESH | Islets of Langerhans/pathology* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred NOD | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Protein Transport | - |
dc.subject.MESH | Tumor Necrosis Factor-alpha/pharmacology* | - |
dc.subject.MESH | bcl-Associated Death Protein | - |
dc.title | Role of Calcium in Pancreatic Islet Cell Death by IFN-γ/TNF-α1 | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학) | - |
dc.contributor.googleauthor | Inik Chang | - |
dc.contributor.googleauthor | Namjoo Cho | - |
dc.contributor.googleauthor | Myung-Shik Lee | - |
dc.contributor.googleauthor | Sung Joon Kim | - |
dc.contributor.googleauthor | Joo Hyun Nam | - |
dc.contributor.googleauthor | Ji-Eun Woo | - |
dc.contributor.googleauthor | Eunshil Kim | - |
dc.contributor.googleauthor | Ja Young Kim | - |
dc.contributor.googleauthor | Sunshin Kim | - |
dc.identifier.doi | 10.4049/jimmunol.172.11.7008 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03461 | - |
dc.relation.journalcode | J01450 | - |
dc.identifier.eissn | 1550-6606 | - |
dc.identifier.pmid | 15153522 | - |
dc.contributor.alternativeName | Chang, In Ik | - |
dc.contributor.affiliatedAuthor | Chang, In Ik | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 172 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 7008 | - |
dc.citation.endPage | 7014 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, Vol.172(11) : 7008-7014, 2004 | - |
dc.identifier.rimsid | 36852 | - |
dc.type.rims | ART | - |
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