[Effects of W-7 on the expression of GRP78 and neuronal apoptosis in immature rat hippocampus after status convulsion].

Abstract

OBJECTIVE:

To 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).

METHODS:

One 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).

RESULTS:

The 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).

CONCLUSIONS:

W-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.

• Authors: Zhu-Ying Zhou, Guang-Qian Li
• Journal: Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics (Zhongguo Dang Dai Er Ke Za Zhi) Vol. 13 Issue 1 Pg. 44-9 (Jan 2011) ISSN: 1008-8830 [Print] China
• PMID: 21251387 (Publication Type: Journal Article)

Chemical References

• GRP78 protein, rat
• Heat-Shock Proteins
• RNA, Messenger
• Sulfonamides
• W 7
• Calcium-Calmodulin-Dependent Protein Kinase Kinase

Topics

• 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)