Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

Autor: Craig T. Ajmo, Hilary A. Seifert, Stephanie M. Davis, Christopher C. Leonardo, Lisa A. Collier, Keith R. Pennypacker
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
endocrine system
Programmed cell death
Small interfering RNA
SOD3
Neuroscience (miscellaneous)
Leukemia Inhibitory Factor
Neuroprotection
Article
Superoxide dismutase
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Downregulation and upregulation
In vivo
Animals
Medicine
Cells
Cultured
reproductive and urinary physiology
Cerebral Cortex
Neurons
Dose-Response Relationship
Drug
biology
Superoxide Dismutase
urogenital system
business.industry
Molecular biology
Cell Hypoxia
Rats
Up-Regulation
3. Good health
Stroke
Neuroprotective Agents
030104 developmental biology
Neurology
Oxidative stress
embryonic structures
biology.protein
business
Leukemia inhibitory factor
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Zdroj: Molecular Neurobiology
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-015-9587-2
Popis: Leukemia inhibitory factor (LIF) has been shown to protect oligodendrocytes from ischemia by upregulating endogenous antioxidants. The goal of this study was to determine whether LIF protects neurons during stroke by upregulating superoxide dismutase 3 (SOD3). Animals were administered phosphate-buffered saline (PBS) or 125 μg/kg LIF at 6, 24, and 48 h after middle cerebral artery occlusion or sham surgery. Neurons were isolated from rat pups on embryonic day 18 and used between 7 and 15 days in culture. Cells were treated with LIF and/or 10 μM Akt inhibitor IV with PBS and 0.1 % DMSO acting as vehicle controls. Neurons transfected with scrambled or SOD3 small interfering RNA (siRNA) were subjected to 24-h ischemia after PBS or LIF treatment. LIF significantly increased superoxide dismutase activity and SOD3 expression in ipsilateral brain tissue compared to PBS. Following 24-h ischemia, LIF reduced cell death and increased SOD3 messenger RNA (mRNA) in vitro compared to PBS. Adding Akt inhibitor IV with LIF counteracted the decrease in cell death. Partially silencing the expression of SOD3 using siRNA prior to LIF treatment counteracted the protective effect of LIF-alone PBS treatment. These results indicate that LIF protects neurons in vivo and in vitro via upregulation of SOD3.
Databáze: OpenAIRE
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