title: Huntingtin is degraded to small fragments by calpain after ischemic injury.
abstract: The gene defect in Huntington's disease (HD) causes a polyglutamine expansion in the N-terminal region of huntingtin (N-htt). In vitro studies suggest that mutant N-htt fragments can aggregate and cause cell death in HD. The physiological and pathological conditions that affect htt proteolysis in the brain are unclear. We examined htt expression by Western blot in the rat brain after transient ischemic injury, which causes striatal neurodegeneration similar to that seen in HD and activates proteases including calcium-dependent calpains. Focal brain ischemia reduced levels of full-length htt in the infarcted cortex and striatum and increased expression of a 55-kDa N-htt fragment that was also produced by treating control brain extracts with calpain. N-htt fragments between 65 and 80 kDa also rose after injury, but these fragments were not as long-lived as the 55-kDa N-htt fragment. The results suggest that after ischemic injury full-length htt is degraded in degenerating neurons and an N-htt fragment accumulates.
authors.affiliation: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Yoon
authors.forename: Lami
authors.initials: L
authors.lastname: Kang
authors.forename: Yun J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Neil
authors.initials: N
authors.lastname: Aronin
authors.forename: Marian
authors.initials: M
authors.lastname: DiFiglia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000378:metabolism*; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D000071058:Huntingtin Protein; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D002154:Calpain