Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum.
The present study investigated the role of lysosomal enzymes in excitotoxic neuronal damage induced by excessive stimulation of non-NMDA glutamate receptors with kainic acid (KA). Internucleosomal DNA fragmentation was induced after intrastriatal administration of KA 1.25-5.0 nmol to rats. Increased expression of cathepsin B (P < 0.01, n = 6) but not cathepsin L in KA-injected striatum was observed 12 to 24 h after intrastriatal infusion of KA (2.5 nmol). Treatment with intrastriatal infusion of the cathepsin B inhibitor Z-FA-FMK (5-10 microg) 10 min prior to or 3 h after KA injection robustly attenuated KA-induced (2.5 nmol) DNA fragmentation. Z-FA-FMK (10 microg) also significantly reduced the size of striatal lesions induced by KA (P < 0.01, n = 6). These results suggest that lysosomal enzyme cathepsin B plays an important role in excitotoxic neuronal injury.
Wang
Yan
Y
Department of Pharmacology, Soochow University School of Medicine, 708 Ren Min Road, Suzhou 215007, PR China.
Gu
Zhen-Lun
ZL
Cao
Yi
Y
Liang
Zhong-Qin
ZQ
Han
Rong
R
Bennett
M Catherine
MC
Qin
Zheng-Hong
ZH
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries; D053938:DNA Fragmentation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity*; D007659:Ketones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004151:Dipeptides; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007659:Ketones; C057383:MDL 201053; D002401:Cathepsin B; D007608:Kainic Acid