title: Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways.
abstract: Poly (ADP-ribose) polymerase-1 (PARP-1) plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ischemia-reperfusion induced cell death has triggered more and more attention. Here, we examined the protective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion (OGDR) model of primary rat astrocytes in vitro, which could mimic the ischemia-reperfusion damage in the "ischemic core". Meanwhile, cell death pathways of various PJ34 treated astrocytes were also investigated. Our results showed that PJ34 incubation (10 μmol/L) did not affect release of lactate dehydrogenase (LDH) from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, PJ34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apoptotic rate. The intervention timing study demonstrated that an earlier and longer PJ34 intervention during reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the "ischaemic core" mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China.|Research Centre for Neural Engineering, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China.|Research Centre for Neural Engineering, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China.|Research Centre for Neural Engineering, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
authors.forename: Qiao-Ying
authors.initials: QY
authors.lastname: Huang
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China.
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Zou
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China. chuxiaofan@hotmail.com.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Chu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D045022:Lactate Dehydrogenases; D005947:Glucose; D010100:Oxygen