TY - JOUR
T1 - Neuroglobin protects PC12 cells against oxidative stress
AU - Li, Richard C.
AU - Morris, Matthew W.
AU - Lee, Seung Kwan
AU - Pouranfar, Farzan
AU - Wang, Yang
AU - Gozal, David
N1 - Funding Information:
We thank Kenneth R. Brittian and Heather B. Clair for their expert technical assistance in cell culture and immunocytochemistry. This study was supported by National Institutes of Health grants SCOR 2P50-HL-60296 (Project 2) and RO1-HL-69932, The Children's Foundation Endowment for Sleep Research, and by the Commonwealth of Kentucky Challenge for Excellence Trust Fund.
PY - 2008/1/23
Y1 - 2008/1/23
N2 - Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12 cells were transfected with wild type and mutant (H64 V/H96A) Ngb for 48 h and then treated with H2O2 (0.1, 0.2 and 0.4 mM) for 6 h. Ngb siRNA decreased the H2O2-induced Ngb expression and exacerbated H2O2-induced cell injury. Transient transfection of Ngb induced dose-dependent increases in Ngb protein expression and did not alter SOD, GPX, and catalase activities. Overexpression of wild type Ngb, but not of mutant Ngb, significantly attenuated H2O2-induced ROS/RNS accumulation and lipid peroxidation, decreased H2O2-induced mitochondrial dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a protective role against oxidative stress, which appears to be primarily mediated by intrinsic Ngb antioxidant properties.
AB - Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12 cells were transfected with wild type and mutant (H64 V/H96A) Ngb for 48 h and then treated with H2O2 (0.1, 0.2 and 0.4 mM) for 6 h. Ngb siRNA decreased the H2O2-induced Ngb expression and exacerbated H2O2-induced cell injury. Transient transfection of Ngb induced dose-dependent increases in Ngb protein expression and did not alter SOD, GPX, and catalase activities. Overexpression of wild type Ngb, but not of mutant Ngb, significantly attenuated H2O2-induced ROS/RNS accumulation and lipid peroxidation, decreased H2O2-induced mitochondrial dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a protective role against oxidative stress, which appears to be primarily mediated by intrinsic Ngb antioxidant properties.
KW - Neuroglobin
KW - Oxidative stress
KW - PC12 cell
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U2 - 10.1016/j.brainres.2007.11.022
DO - 10.1016/j.brainres.2007.11.022
M3 - Article
C2 - 18083144
AN - SCOPUS:37549003333
VL - 1190
SP - 159
EP - 166
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -