Effects of W-7 on the expression of GRP78 and neuronal apoptosis in immature rat hippocampus after status convulsion.
- Author:
Zhu-Ying ZHOU
1
;
Guang-Qian LI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Calcium-Calmodulin-Dependent Protein Kinase Kinase; antagonists & inhibitors; Heat-Shock Proteins; genetics; Hippocampus; metabolism; In Situ Nick-End Labeling; Male; Neurons; drug effects; RNA, Messenger; analysis; Rats; Rats, Sprague-Dawley; Status Epilepticus; metabolism; Sulfonamides; pharmacology
- From: Chinese Journal of Contemporary Pediatrics 2011;13(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of the calmodulin inhibitor W-7 on the expression of the key marker of ERS GRP78 and neuronal apoptosis in the immature rat hippocampus after status convulsion (SC).
METHODSOne hundred and seventeen male Sprague-Dawley rats aged 19-21 days were randomly divided into three groups: normal saline control (control), SC with and without W-7 pretreatment. Each of the 3 groups was further subdivided into subgroups sacrificed at 4, 24 and 48 hrs. SC model was prepared using lithium-pilocarpine. GRP78 mRNA expression in the hippocampus was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). GRP78 protein was ascertained by immunohistochemistry. Neuronal apoptosis was observed with TdT-mediated dUTP nick end labeling (TUNEL).
RESULTSThe expression of GRP78 mRNA was significantly increased in the non-pretreated SC group compared with the control group 24 hrs after injection of saline or lithium-pilocarpine (P<0.01), and the expression of GRP78 protein also increased markedly in the seizure group compared with the control group 24 and 48 hrs after the injection (P<0.01). The expression of GRP78 mRNA and protein in the W-7 pretreatment group was significantly higher than both the control and the non-pretreated seizure groups 24 and 48 hrs after injection. The TUNEL positive cells in the hippocampus CA1 in the non-pretreated SC group 24 and 48 hrs after injection (21.0 ± 2.5 and 29.4 ± 2.8, respectively) were increased compared to the control group (7.1 ± 1.4 and 7.3 ± 1.6, respectively; P<0.01). W-7 pretreatment decreased TUNEL positive cells to 15.0 ± 2.5 and 20.0 ± 2.9 at 24 and 48 hrs after injection compared to the non-pretreated seizure group (P<0.01), but the number of TUNEL positive cells in the W-7 pretreatment group remained significantly greater than in the control group (P<0.01).
CONCLUSIONSW-7 may up-regulate the expression of GRP78 and reduce the number of apoptotic neurons, thus provides a neuroprotective effect against brain damage following SC.
