Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways.
10.1007/s11596-015-1444-z
- Author:
Chuan CAI
1
;
Rui ZHANG
;
Qiao-Ying HUANG
;
Xu CAO
;
Liang-Yu ZOU
;
Xiao-Fan CHU
Author Information
1. Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, China, yuanzihe1985@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
Astrocytes;
cytology;
drug effects;
Cell Survival;
Cells, Cultured;
Glucose;
deficiency;
Humans;
Lactate Dehydrogenases;
metabolism;
Male;
Models, Biological;
Oxygen;
metabolism;
Phenanthrenes;
pharmacology;
Poly(ADP-ribose) Polymerase Inhibitors;
pharmacology;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
drug effects
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(3):397-404
- CountryChina
- Language:English
-
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.
