Neuroglobin protects PC12 cells against oxidative stress.
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.
Li
Richard C
RC
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Morris
Matthew W
MW
Lee
Seung Kwan
SK
Pouranfar
Farzan
F
Wang
Yang
Y
Gozal
David
D
D000818:Animals; D016923:Cell Death / Q000502:physiology; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014162:Transfection
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D005914:Globins; D006861:Hydrogen Peroxide