Abstracts from the 4th Global Chinese Symposium and the 8th Symposium for cross-straits, Hong Kong and Macao on free rad
- PDF / 873,759 Bytes
- 5 Pages / 595.276 x 790.866 pts Page_size
- 33 Downloads / 137 Views
MEETING ABSTRACTS
Chinese Medicine Open Access
Abstracts from 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 Published: 26 November 2018
A1 Peroxynitrite‑mediated mitophagy could be a crucial therapeutic target for reducing cerebral ischemia–reperfusion injury Jiangang Shen, Jinghan Feng, Hansen Chen School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Hong Kong, SAR, China Correspondence: Jiangang Shen ‑ [email protected] Journal of Chinese Medicine 2018, 13(Supp 2):A1 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 oxygenglucose-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, peroxyn
Data Loading...
