title: Proteinase 3 induces oxidative stress-mediated neuronal death in rat primary cortical neuron.
abstract: The recruitment of neutrophils into the cerebral microcirculation occurs, especially, in acute brain diseases like a focal cerebral ischemia and plays important role in pathological processes. Proteinase 3 is one of the three major proteinases expressed in neutrophils but no reports are available whether proteinase 3 can modulate neuronal survival. In this study, treatment of cultured rat primary cortical neuron with proteinase 3 induced overt reactive oxygen species production and decreased total glutathione contents as well as disruption of mitochondrial transmembrane potential. Proteinase 3 induced neuronal cell death as evidenced by MTT analysis as well as propidium iodide staining, which was prevented by pretreatment with an antioxidant, N-acetyl cysteine. Proteinase 3 increased activation of procaspase-3 and altered expression level of apoptotic regulator proteins, such as Bcl-2, Bax, and Bcl-xL. Similar to in vitro data, a direct microinjection of proteinase 3 into striatum of rat brain induced neuronal death, which was mediated by reactive oxygen species. These results suggest that proteinase 3 is new essential regulator of neuronal cell death pathway in a condition of excess neutrophil encounter in neuroinflammatory conditions.
authors.affiliation: Department of Neurology, Institute of Advanced Biomedical Science, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Kyoung Ja
authors.initials: KJ
authors.lastname: Kwon
authors.forename: Kyu Suk
authors.initials: KS
authors.lastname: Cho
authors.forename: Jung Nam
authors.initials: JN
authors.lastname: Kim
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Ki Chan
authors.initials: KC
authors.lastname: Kim
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Han
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Soohyun
authors.initials: S
authors.lastname: Kim
authors.forename: Hahn Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Seol-Heui
authors.initials: SH
authors.lastname: Han
authors.forename: Geonho
authors.initials: G
authors.lastname: Bahn
authors.forename: Ji woong
authors.initials: Jw
authors.lastname: Choi
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D008297:Male; D053146:Myeloblastin / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D053146:Myeloblastin
keywords: Apoptosis; Neuron; Neutrophil; Proteinase 3; ROS