title: Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum.
abstract: 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.
authors.affiliation: Department of Pharmacology, Soochow University School of Medicine, 708 Ren Min Road, Suzhou 215007, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhen-Lun
authors.initials: ZL
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhong-Qin
authors.initials: ZQ
authors.lastname: Liang
authors.forename: Rong
authors.initials: R
authors.lastname: Han
authors.forename: M Catherine
authors.initials: MC
authors.lastname: Bennett
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Qin
mesh_terms: 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
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007659:Ketones; C057383:MDL 201053; D002401:Cathepsin B; D007608:Kainic Acid