TY - JOUR
T1 - Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam
AU - Choi, Young
AU - Jin, Youngnam
AU - Nam, Wonwoo
AU - Kim, Hyoung Chun
AU - Kim, Won Ki
N1 - Funding Information:
This work was supported by a grant (#1999-2-207-007-3) of the Korea Science and Engineering Foundation and the Neurobiology Research Program from the Korea Ministry of Science and Technology, Republic of Korea. I.Y. Choi is the recipient of Research Fellowship (Brain Korea 21 Project).
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Under glucose-deprived conditions, astrocytes rapidly underwent death due to their increased susceptibility to endogenously produced peroxynitrite (Gila 31, 155-164; J. Neuroimmunol. 112, 55-62; J. Neurochem. 74, 1989-1998). In the present study, the cell membrane-permeable synthetic superoxide dismutase (SOD) mimetic cyclam manganese(III) 1,4,8,11-tetraazacyclodecane (Mn(III)-cyclam) completely inhibited the death of glucose-deprived immunostimulated astrocytes. However, the structurally related compounds Ni(II)-cyclam, Co(II)-cyclam, and H2-cyclam, which lacks metals, had no or a little cytoprotective effect. Of the cyclams used in this study, only Mn(III)-cyclam completely scavenged the peroxynitrite produced in glucose-deprived immunostimulated astrocytes and significantly blocked the depolarization of mitochondrial transmembrane potential in those cells. The present results suggest that cell membrane-permeable synthetic SOD mimetics such as Mn(III)-cyclam may be potential therapeutic agents for various diseases associated with the endogenous production of peroxynitrite.
AB - Under glucose-deprived conditions, astrocytes rapidly underwent death due to their increased susceptibility to endogenously produced peroxynitrite (Gila 31, 155-164; J. Neuroimmunol. 112, 55-62; J. Neurochem. 74, 1989-1998). In the present study, the cell membrane-permeable synthetic superoxide dismutase (SOD) mimetic cyclam manganese(III) 1,4,8,11-tetraazacyclodecane (Mn(III)-cyclam) completely inhibited the death of glucose-deprived immunostimulated astrocytes. However, the structurally related compounds Ni(II)-cyclam, Co(II)-cyclam, and H2-cyclam, which lacks metals, had no or a little cytoprotective effect. Of the cyclams used in this study, only Mn(III)-cyclam completely scavenged the peroxynitrite produced in glucose-deprived immunostimulated astrocytes and significantly blocked the depolarization of mitochondrial transmembrane potential in those cells. The present results suggest that cell membrane-permeable synthetic SOD mimetics such as Mn(III)-cyclam may be potential therapeutic agents for various diseases associated with the endogenous production of peroxynitrite.
KW - Glucose deprivation
KW - Immunostimulation
KW - Mitochondria transmembrane potential
KW - Mn(III)-cyclam
UR - http://www.scopus.com/inward/record.url?scp=0037304924&partnerID=8YFLogxK
U2 - 10.1016/S0168-0102(02)00206-7
DO - 10.1016/S0168-0102(02)00206-7
M3 - Article
C2 - 12573462
AN - SCOPUS:0037304924
SN - 0168-0102
VL - 45
SP - 157
EP - 161
JO - Neuroscience Research
JF - Neuroscience Research
IS - 2
ER -