Intervention Timing and Effect of PJ34 on Astrocytes During Oxygen-glucose Deprivation/reperfusion and Cell Death Pathways

Overview

Journal J Huazhong Univ Sci Technolog Med Sci

Specialty General Medicine

Date 2015 Jun 15

PMID 26072080

Citations 1

Authors

Chuan Cai

Rui Zhang

Qiao-ying Huang

Xu Cao

Liang-Yu Zou

Xiao-Fan Chu

Affiliations

Soon will be listed here.

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.

Citing Articles

Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain.

Bonnin P, Vitalis T, Schwendimann L, Boutigny A, Mohamedi N, Besson V Curr Issues Mol Biol. 2021; 43(1):301-312.

PMID: 34200155 PMC: 8929080. DOI: 10.3390/cimb43010025.

References

Montgomery D . Astrocytes: form, functions, and roles in disease. Vet Pathol. 1994; 31(2):145-67. DOI: 10.1177/030098589403100201. View

Del Nagro C, Xiao Y, Rangell L, Reichelt M, OBrien T . Depletion of the central metabolite NAD leads to oncosis-mediated cell death. J Biol Chem. 2014; 289(51):35182-92. PMC: 4271207. DOI: 10.1074/jbc.M114.580159. View

Giffard R, Xu L, Zhao H, Carrico W, Ouyang Y, Qiao Y . Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury. J Exp Biol. 2004; 207(Pt 18):3213-20. DOI: 10.1242/jeb.01034. View

Benjelloun N, Joly L, Palmier B, Plotkine M, Charriaut-Marlangue C . Apoptotic mitochondrial pathway in neurones and astrocytes after neonatal hypoxia-ischaemia in the rat brain. Neuropathol Appl Neurobiol. 2003; 29(4):350-60. DOI: 10.1046/j.1365-2990.2003.00467.x. View

Walisser J, Thies R . Poly(ADP-ribose) polymerase inhibition in oxidant-stressed endothelial cells prevents oncosis and permits caspase activation and apoptosis. Exp Cell Res. 1999; 251(2):401-13. DOI: 10.1006/excr.1999.4589. View

Zakeri Z, Bursch W, Tenniswood M, Lockshin R . Cell death: programmed, apoptosis, necrosis, or other?. Cell Death Differ. 1995; 2(2):87-96. View

Nagayama T, Simon R, Chen D, Henshall D, Pei W, Stetler R . Activation of poly(ADP-ribose) polymerase in the rat hippocampus may contribute to cellular recovery following sublethal transient global ischemia. J Neurochem. 2000; 74(4):1636-45. DOI: 10.1046/j.1471-4159.2000.0741636.x. View

Giffard R, Swanson R . Ischemia-induced programmed cell death in astrocytes. Glia. 2005; 50(4):299-306. DOI: 10.1002/glia.20167. View

Zhang R, Huang Q, Zou L, Cao X, Huang H, Chu X . Beneficial effects of deferoxamine against astrocyte death induced by modified oxygen glucose deprivation. Brain Res. 2014; 1583:23-33. DOI: 10.1016/j.brainres.2014.08.016. View

10.

Abdelkarim G, Gertz K, Harms C, Katchanov J, Dirnagl U, Szabo C . Protective effects of PJ34, a novel, potent inhibitor of poly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke. Int J Mol Med. 2001; 7(3):255-60. View

11.

Kern J, Kehrer J . Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact. 2002; 139(1):79-95. DOI: 10.1016/s0009-2797(01)00295-2. View

12.

Weerasinghe P, Buja L . Oncosis: an important non-apoptotic mode of cell death. Exp Mol Pathol. 2012; 93(3):302-8. DOI: 10.1016/j.yexmp.2012.09.018. View

13.

Salvesen G . Caspases: opening the boxes and interpreting the arrows. Cell Death Differ. 2002; 9(1):3-5. DOI: 10.1038/sj.cdd.4400963. View

14.

Wani W, Sunkaria A, Sharma D, Kandimalla R, Kaushal A, Gerace E . Caspase inhibition augments Dichlorvos-induced dopaminergic neuronal cell death by increasing ROS production and PARP1 activation. Neuroscience. 2013; 258:1-15. DOI: 10.1016/j.neuroscience.2013.11.004. View

15.

Cao X, Zhang Y, Zou L, Xiao H, Chu Y, Chu X . Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and calpain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis. Neurosci Lett. 2010; 479(2):118-22. DOI: 10.1016/j.neulet.2010.05.040. View

16.

Sun L, Zhao Y, Yuan H, Li X, Cheng A, Lou H . Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells. Cancer Chemother Pharmacol. 2010; 67(4):813-21. DOI: 10.1007/s00280-010-1387-9. View

17.

Jugdutt B, Idikio H . Apoptosis and oncosis in acute coronary syndromes: assessment and implications. Mol Cell Biochem. 2005; 270(1-2):177-200. DOI: 10.1007/s11010-005-4507-9. View

18.

Jagtap P, Szabo C . Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov. 2005; 4(5):421-40. DOI: 10.1038/nrd1718. View

19.

Eliasson M, Sampei K, Mandir A, Hurn P, Traystman R, Bao J . Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med. 1997; 3(10):1089-95. DOI: 10.1038/nm1097-1089. View

20.

Chu X, Fu X, Zou L, Qi C, Li Z, Rao Y . Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia. Brain Res. 2007; 1149:157-64. DOI: 10.1016/j.brainres.2007.02.061. View