Neuroprotective effects of a novel poly (ADP-ribose) polymerase-1 inhibitor, JPI-289, in hypoxic rat cortical neurons
DC Field | Value | Language |
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dc.contributor.author | Kim, Youngchul | - |
dc.contributor.author | Kim, Young S. | - |
dc.contributor.author | Noh, Min-Young | - |
dc.contributor.author | Lee, Hanchang | - |
dc.contributor.author | Joe, Boyoung | - |
dc.contributor.author | Kim, Hyun Y. | - |
dc.contributor.author | Kim, Jeongmin | - |
dc.contributor.author | Kim, Seung H. | - |
dc.contributor.author | Park, Jiseon | - |
dc.date.accessioned | 2022-07-14T02:00:04Z | - |
dc.date.available | 2022-07-14T02:00:04Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.issn | 0305-1870 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/152263 | - |
dc.description.abstract | Excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischaemic brain injury. Therefore, PARP-1 inhibition after ischaemic stroke has been attempted in successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischaemic injury in an in vitro model. The half-life of JPI-289 after intravenous or oral administration in rats was relatively long (1.4-1.5 hours) with 65.6% bioavailability. The inhibitor strongly inhibited PARP-1 activity (IC50=18.5 nmol/L) and cellular PAR formation (IC50=10.7 nmol/L) in the nanomolar range. In rat cortical neuronal cells, JPI-289 did not affect cell viability up to 1 mmol/L as assayed by Trypan blue staining (TBS) and lactate dehydrogenase (LDH) assay. Treatment of JPI-289 for 2 hours after 2 hours of oxygen glucose deprived (OGD) rat cortical neuron attenuated PARP activity and restored ATP and NAD+ levels. Apoptosis-associated molecules such as apoptosis inducing factor (AIF), cytochrome C and cleaved caspase-3 were reduced after JPI-289 treatment in the OGD model. The present findings suggest that the novel PARP-1 inhibitor, JPI-289, is a potential neuroprotective agent which could be useful as a treatment for acute ischaemic stroke. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.title | Neuroprotective effects of a novel poly (ADP-ribose) polymerase-1 inhibitor, JPI-289, in hypoxic rat cortical neurons | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Young S. | - |
dc.contributor.affiliatedAuthor | Kim, Hyun Y. | - |
dc.contributor.affiliatedAuthor | Kim, Seung H. | - |
dc.identifier.doi | 10.1111/1440-1681.12757 | - |
dc.identifier.scopusid | 2-s2.0-85019572791 | - |
dc.identifier.wosid | 000404275300008 | - |
dc.identifier.bibliographicCitation | CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, v.44, no.6, pp.671 - 679 | - |
dc.relation.isPartOf | CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | - |
dc.citation.title | CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | - |
dc.citation.volume | 44 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 671 | - |
dc.citation.endPage | 679 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.subject.keywordPlus | IN-VIVO MODELS | - |
dc.subject.keywordPlus | POLY(ADP-RIBOSE) POLYMERASE-1 | - |
dc.subject.keywordPlus | CEREBRAL-ISCHEMIA | - |
dc.subject.keywordPlus | PARP INHIBITOR | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | VITRO | - |
dc.subject.keywordPlus | MINOCYCLINE | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | STROKE | - |
dc.subject.keywordPlus | NAD(+) | - |
dc.subject.keywordAuthor | cerebral ischaemia | - |
dc.subject.keywordAuthor | PARP-1 inhibitor | - |
dc.subject.keywordAuthor | stroke | - |
dc.identifier.url | https://onlinelibrary.wiley.com/doi/10.1111/1440-1681.12757 | - |
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