Involvement of brain CYP2 E1 in damage to neuronal cells induced by lipopolysaccharide
10.3969/j.issn.1001-1978.2016.07.010
- VernacularTitle:脑 CYP2 E1参与脂多糖诱导的神经元损伤
- Author:
Shufang NA
;
Hui YAO
;
Jie LI
;
Zheqiong YANG
;
Jiang YUE
- Publication Type:Journal Article
- Keywords:
cytochrome P450 2E1;
lipopolysaccha-ride;
inflammation;
neuron;
ERK signaling pathway;
p38 signaling pathway
- From:
Chinese Pharmacological Bulletin
2016;32(7):932-937
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the interactions be-tween the neuroinflammation caused by lipopolysaccha-ride(LPS) and brain CYP2E1.Methods The human cholinergic neuroblastoma cell line IMR-32 was treated with LPS ( 0.1 mg · L-1 , 1.0 mg · L-1 ) , and the LDH and SOD activities were determined after 24 h in-cubation .In order to determine the roles of MAPK sig-naling pathway in the regulation of CYP 2E1 by LPS, the IMR-32 cells were treated with p38 pathway inhibi-tor SB203580 or ERK pathway inhibitor U 0126 for 45 min before the incubation with LPS .The human do-paminergic neuroblastoma cell line SH-SY5Y with CYP2 E1 over-expression was established . The LDH and SOD activities were determined in SH-SY5 Y cells over-expressed CYP2 E1 and control cells treated with LPS(0.1 mg· L-1 , 1.0 mg· L-1 ) for 24 h.Results
The levels of LDH in IMR-32 cells treated with high-dose LPS were increased by 1.38-fold ( P <0.01 ) compared with the control group , and the levels of SOD reduced by 15.0%( P <0.01 ) .Compared with the control, CYP2E1 mRNA and protein levels in IMR-32 cells treated with high-dose LPS were increased by 1.25-fold(P<0.01) and 1.19-fold(P<0.05).The up-regulation of CYP2E1 by LPS could be attenuated by SB203580 and U0126 pretreatment.Compared with the control cells, the CYP2E1 over-expression in-creased LDH levels by 1.28-fold ( P<0.01 ) and de-creased SOD levels by 3.53-fold ( P<0.01 ) after the low-dose of LPS treatment .The CYP2E1 over-expres-sion increased LDH levels by 1.54-fold ( P <0.01 ) and decreased SOD levels by 2.17-fold( P<0.01) af-ter the high-dose of LPS treatment , compared with the control cells.Conclusions LPS can induce CYP2E1 mRNA and protein levels , and the p38 and ERK sig-naling pathway may be involved in the regulation .The elevated CYP2 E1 levels aggravate the damage to neuro-nal cells caused by LPS .Brain CYP2E1 may be an im-portant contributing factor to the pathological process of neuroinflammatory injury .
