Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam

Young Choi; Youngnam Jin; Wonwoo Nam; Hyoung Chun Kim; Won Ki Kim

doi:10.1016/S0168-0102(02)00206-7

Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam

Young Choi, Youngnam Jin, Wonwoo Nam, Hyoung Chun Kim, Won Ki Kim

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	157-161
Number of pages	5
Journal	Neuroscience Research
Volume	45
Issue number	2
DOIs	https://doi.org/10.1016/S0168-0102(02)00206-7
State	Published - 1 Feb 2003

Bibliographical note

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).

Keywords

Glucose deprivation
Immunostimulation
Mitochondria transmembrane potential
Mn(III)-cyclam

Access to Document

10.1016/S0168-0102(02)00206-7

Cite this

@article{550e24141deb4ca1b5ff49847364d8bd,

title = "Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam",

abstract = "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.",

keywords = "Glucose deprivation, Immunostimulation, Mitochondria transmembrane potential, Mn(III)-cyclam",

author = "Young Choi and Youngnam Jin and Wonwoo Nam and Kim, {Hyoung Chun} and Kim, {Won Ki}",

note = "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).",

year = "2003",

month = feb,

day = "1",

doi = "10.1016/S0168-0102(02)00206-7",

language = "English",

volume = "45",

pages = "157--161",

journal = "Neuroscience Research",

issn = "0168-0102",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

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 -

Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this