Alpha-synuclein expression is up-regulated in NTera2 cells during neuronal differentiation but unaffected by exposure to cytokines and neurotrophic factors.
Increasing evidence has indicated that proinflammatory cytokines such as TNF-alpha and IL-1beta, produced by activated microglia and astrocytes, play a key role in progressive degeneration of the nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Since alpha-synuclein is a major component of Lewy bodies in PD brains, we studied the constitutive and cytokine/neurotrophic factor-regulated expression of alpha-synuclein in cultured human neurons by Northern blot and Western blot analyses. The constitutive expression of alpha-synuclein mRNA was identified in a variety of human neural and non-neural cell lines. The levels of alpha-synuclein expression were elevated markedly in NTera2 teratocarcinoma cells following retinoic acid-induced neuronal differentiation, accompanied with an increased expression of synphilin-1, while they were unaltered in NTera2-derived differentiated neurons by exposure to TNF-alpha, IL-1beta, BDNF or GDNF. These results indicate that alpha-synuclein expression in human neurons is up-regulated during differentiation, but is unaffected by a panel of cytokines and neurotrophic factors which are supposed to be involved in the nigral neuronal death and survival.
Satoh
J I
JI
Division of Neurology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima 849-8501, Japan. satojl@post.saga-med.ac.jp
Kuroda
Y
Y
D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051843:Synucleins; D018243:Teratocarcinoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051844:alpha-Synuclein
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007375:Interleukin-1; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein