Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6282965 | Neuroscience Letters | 2013 | 6 Pages |
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.
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Authors
Kyoung Ja Kwon, Kyu Suk Cho, Jung Nam Kim, Min Kyeong Kim, Eun Joo Lee, Soo Young Kim, Se Jin Jeon, Ki Chan Kim, Jeong Eun Han, Young Sun Kang, Soohyun Kim, Hahn Young Kim, Seol-Heui Han, Geonho Bahn, Ji woong Choi, Chan Young Shin,