title: Anti-necroptosis chemical necrostatin-1 can also suppress apoptotic and autophagic pathway to exert neuroprotective effect in mice intracerebral hemorrhage model.
abstract: Necroptosis was recently discovered as one form of programmed cell death (PCD) and could be specifically inhibited by necrostatin-1. The aim of this study was to examine the effect of necrostatin-1 on brain injury and investigate the role of necrostatin-1 on the other two types PCD (apoptosis and autophagic cell death) in a mouse intracerebral hemorrhage (ICH) model. Male ICR mice received an infusion of type IV collagenase to induce ICH or saline as control into the left striatum. In the presence of vehicle, 3-MA, zVAD, and necrostatin-1 were pretreated with a single intracerebroventricular (i.c.v.) injection in the ipsilateral ventricle 15 min before ICH, respectively. Compared with vehicle groups, necrostatin-1 treatment significantly reduced injury volume and propidium iodide-positive cells at 24 and 72 h after ICH. Immunoblotting analysis showed that necrostatin-1 treatment suppressed autophagic-associated proteins (LC3-II, Beclin-1) and maintained p62 at normal level at 24 and 72 h after ICH. In addition, necrostatin-1 treatment enhanced the protein level of Bcl-2 and decreased the protein level of cleaved caspase-3 and the Beclin-1/Bcl-2 ratio at 24 and 72 h after ICH. Moreover, both 3-MA and necrostatin-1 treatment could suppress cleaved caspase-3 and LC3-II production, whereas zVAD treatment could inhibit caspase-3 cleavage but increased LC3-II protein levels at 72 h after ICH. Taken together, the data demonstrated for the first time that the specific inhibitor necrostatin-1 suppressed apoptosis and autophagy to exert these neuroprotective effects after ICH and that there existed a cross-talk among necroptosis, apoptosis, and autophagy after ICH.
authors.forename: Pan
authors.initials: P
authors.lastname: Chang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Dong
authors.forename: Mingyang
authors.initials: M
authors.lastname: Zhang
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Meng
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.forename: Chengliang
authors.initials: C
authors.lastname: Luo
authors.forename: Xiping
authors.initials: X
authors.lastname: Chen
authors.forename: Luyang
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D007093:Imidazoles; D007211:Indoles; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C507699:necrostatin-1; C052617:Bcl2 protein, mouse; D053148:Caspase 3