ENDOPLASMIC RETICULUM STRESS RESPONSE IN KAINIC ACID SEIZURE MODEL
Abstract number :
1.101
Submission category :
Year :
2003
Submission ID :
3864
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Yoon Seong Jang, Oh-Joo Kwon Department of Biochemistry, College of Medicine, the Catholic University of Korea, Seoul, Seoul, Republic of Korea
Seizures may cause brain damage due to mechanisms initiated by excessive excitatory synaptic transmission. One such mechanism is the activation of death-promoting intracellular cascades by the influx and the perturbed homeostasis of Ca2+, which leads to dysfunction of intracellular organelles including mitochondria and endoplasmic reticulum (ER). Endoplasmic Reticulum is involved in protein synthesis and early protein modification as well as calcium homeostasis, and disturbance of them causes ER stress responses. Although the molecular mechanism of ER stress response has been studied in some yeasts and cell lines, less clear is the contribution to ER stress response in animal seizure models.
Our animal seizure model was prepared by intraperitoneal injection of 12 mg/kg kainic acid. For determining dose-dependency and involvement of NMDA receptors, we used 4, 8, 12, 16 mg/kg kainic acid and 0.5 to 4 mg/kg MK-801 were used. To investigate ER stress response in the hippocampus of kainic acid-treated rats, we carried out immunohistochemistry and western blotting using anti-Grp78/BiP antibody.
Here we show that endoplasmic reticulum (ER) stress response occurs in kainic acid-induced seizure rats. Grp78/BiP, an inducible chaperone present in endoplasmic reticulum (ER) was expressed in CA1 to CA3 the rat hippocampus after kainate administration. Its changes were time- and dose-dependent. The immunoreactivity was increased from 6 h, sustained by 72 h. More than 10 mg/kg kainic acid induced the immunoreactivity prominently, but less than 8 mg/kg did not. The dentate gyrus showed no changes of BiP immunoreactivity. In addition, pretreatment of MK-801, an NMDA receptor antagonist prevented the neuronal degeneration and the increase of BiP immunoreactivity in CA1 to CA3.
Kainic acid-induced seizure model showed ER stress response in the hippocampus. This response could be compensatory to disturbed ER functions and overloaded demand in protein synthesis in kainic acid-induced excitotoxic conditions.
[Supported by: A grant from the 2001 Basic Medical Science Promotion Program of the Korean Medical Association (Yoon-Seong Jang).]