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Conference Paper: Peroxynitrite‑mediated mitophagy could be a crucial therapeutic target for reducing cerebral ischemia–reperfusion injury
Title | Peroxynitrite‑mediated mitophagy could be a crucial therapeutic target for reducing cerebral ischemia–reperfusion injury |
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Authors | |
Issue Date | 2018 |
Publisher | BioMed Central Ltd. The Abstracts' web site is located at https://cmjournal.biomedcentral.com/articles/10.1186/s13020-018-0212-y |
Citation | The 4th global Chinese Symposium and The 8th Symposium for cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine, Taipa, Macau, 21-24 September 2018. Abstracts in Chinese Medicine, 2018, v. 13 Suppl. 2, p. 56, abstract no. A1 How to Cite? |
Abstract | Basic autophagy/mitophagy is essential for cell survival whereas excessive autophagy/mitophagy is detrimental during cerebral ischemia–reperfusion (I/R) injury. Peroxynitrite (ONOO−), a representative of reactive nitrogen species, is a critical neurotoxic factor in mediating cerebral I/R injury, but its roles in autophagy/mitophagy remain unclear. Herein, we hypothesized that ONOO− could induce PINK1/Parkin-mediated mitophagy activation via triggering dynamin-related protein 1 (Drp1) recruitment to damaged mitochondria, contributing to cerebral I/R injury. The major discoveries revealed that: (1) PINK1/Parkin-mediated mitophagy activation was predominant among general autophagy, leading to rat brain injury at the reperfusion phase after cerebral ischemia; (2) increased nitrotyrosine was found in the plasma of ischemic stroke patients and ischemia–reperfused rat brains, indicating the generation of ONOO− in ischemic stroke; (3) ONOO− was dramatically increased in accompanied with mitochondrial recruitment of Drp1, PINK1/Parkin-mediated mitophagy activation, and progressive infarct size in rat ischemic brains at the reperfusion phase; (4) FeTMPyP, a peroxynitrite decomposition catalyst, remarkably reversed mitochondrial recruitment of Drp1, mitophagy activation and brain injury; (5) ONOO− induced tyrosine nitration of Drp1 peptide and mitochondrial recruitment of Drp1 for mitophagy activation. Those results suggest that ONOO−-induced mitophagy activation aggravates cerebral I/R injury via recruiting Drp1 to damaged mitochondria. Furthermore, we investigated ONOO−-induced mitophagy as a therapeutic target for attenuating cerebral I/R injury by using a natural antioxidant naringin as an example. Naringin possessed strong ONOO− scavenging capability and inhibited the production of superoxide and nitric oxide in SH-SY5Y cells under 10 h oxygen-glucose-deprivation plus 14 h of reoxygenation or ONOO− donor 3-morpholinosydnonimine conditions. Naringin also inhibited NADPH oxidases and iNOS in rat brains with 2 h ischemia plus 22 h reperfusion. Naringin was able to cross the blood–brain barrier, decreased neurological deficit score and infarct size, and attenuated apoptotic cell death. Naringin reduced 3-nitrotyrosine formation, decreased the ratio of LC3-II to LC3-I in mitochondrial fraction, and inhibited the translocation of Parkin to the mitochondria. Taken together, peroxynitrite-mediated mitophagy activation could be a potential therapeutic target for cerebral I/R injury. |
Persistent Identifier | http://hdl.handle.net/10722/262095 |
ISSN | 2023 Impact Factor: 5.3 2023 SCImago Journal Rankings: 0.877 |
DC Field | Value | Language |
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dc.contributor.author | Shen, J | - |
dc.contributor.author | Feng, J | - |
dc.contributor.author | Chen, H | - |
dc.date.accessioned | 2018-09-28T04:53:15Z | - |
dc.date.available | 2018-09-28T04:53:15Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | The 4th global Chinese Symposium and The 8th Symposium for cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine, Taipa, Macau, 21-24 September 2018. Abstracts in Chinese Medicine, 2018, v. 13 Suppl. 2, p. 56, abstract no. A1 | - |
dc.identifier.issn | 1749-8546 | - |
dc.identifier.uri | http://hdl.handle.net/10722/262095 | - |
dc.description.abstract | Basic autophagy/mitophagy is essential for cell survival whereas excessive autophagy/mitophagy is detrimental during cerebral ischemia–reperfusion (I/R) injury. Peroxynitrite (ONOO−), a representative of reactive nitrogen species, is a critical neurotoxic factor in mediating cerebral I/R injury, but its roles in autophagy/mitophagy remain unclear. Herein, we hypothesized that ONOO− could induce PINK1/Parkin-mediated mitophagy activation via triggering dynamin-related protein 1 (Drp1) recruitment to damaged mitochondria, contributing to cerebral I/R injury. The major discoveries revealed that: (1) PINK1/Parkin-mediated mitophagy activation was predominant among general autophagy, leading to rat brain injury at the reperfusion phase after cerebral ischemia; (2) increased nitrotyrosine was found in the plasma of ischemic stroke patients and ischemia–reperfused rat brains, indicating the generation of ONOO− in ischemic stroke; (3) ONOO− was dramatically increased in accompanied with mitochondrial recruitment of Drp1, PINK1/Parkin-mediated mitophagy activation, and progressive infarct size in rat ischemic brains at the reperfusion phase; (4) FeTMPyP, a peroxynitrite decomposition catalyst, remarkably reversed mitochondrial recruitment of Drp1, mitophagy activation and brain injury; (5) ONOO− induced tyrosine nitration of Drp1 peptide and mitochondrial recruitment of Drp1 for mitophagy activation. Those results suggest that ONOO−-induced mitophagy activation aggravates cerebral I/R injury via recruiting Drp1 to damaged mitochondria. Furthermore, we investigated ONOO−-induced mitophagy as a therapeutic target for attenuating cerebral I/R injury by using a natural antioxidant naringin as an example. Naringin possessed strong ONOO− scavenging capability and inhibited the production of superoxide and nitric oxide in SH-SY5Y cells under 10 h oxygen-glucose-deprivation plus 14 h of reoxygenation or ONOO− donor 3-morpholinosydnonimine conditions. Naringin also inhibited NADPH oxidases and iNOS in rat brains with 2 h ischemia plus 22 h reperfusion. Naringin was able to cross the blood–brain barrier, decreased neurological deficit score and infarct size, and attenuated apoptotic cell death. Naringin reduced 3-nitrotyrosine formation, decreased the ratio of LC3-II to LC3-I in mitochondrial fraction, and inhibited the translocation of Parkin to the mitochondria. Taken together, peroxynitrite-mediated mitophagy activation could be a potential therapeutic target for cerebral I/R injury. | - |
dc.language | eng | - |
dc.publisher | BioMed Central Ltd. The Abstracts' web site is located at https://cmjournal.biomedcentral.com/articles/10.1186/s13020-018-0212-y | - |
dc.relation.ispartof | The Global Chinese Symposium and The Symposium for cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine | - |
dc.relation.ispartof | Chinese Medicine | - |
dc.title | Peroxynitrite‑mediated mitophagy could be a crucial therapeutic target for reducing cerebral ischemia–reperfusion injury | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Chen, H: chenhs@hku.hk | - |
dc.identifier.email | Shen, J: shenjg@hku.hk | - |
dc.identifier.authority | Shen, J=rp00487 | - |
dc.identifier.hkuros | 293263 | - |
dc.identifier.hkuros | 296298 | - |
dc.identifier.hkuros | 296706 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1749-8546 | - |