Ubiquitin C-terminal hydrolase-L1 (PGP9.5) expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines, neurotrophic factors or heat stress.
Dysfunction of the ubiquitin-dependent proteolytic pathway contributes to progressive accumulation of ubiquitinated protein inclusions in neurodegenerative disorders, such as Parkinson's disease (PD). Ubiquitin C-terminal hydrolase-L1 (UCH-L1), alternatively designated protein gene product 9.5 (PGP9.5), is a neural deubiquitinating enzyme which is identified as a principal constituent of Lewy bodies. To clarify the regulatory mechanism of UCH-L1 expression in human neural cells, we studied the constitutive, cytokine/neurotrophic factor-regulated, and heat stress-induced expression of UCH-L1 in cultured human neural cell lines by Western blot analysis. The constitutive expression of UCH-L1 was identified in SK-N-SH neuroblastoma cells, IMR-32 neuroblastoma cells, U-373MG astrocytoma cells, and NTera2 teratocarcinoma-derived differentiated neurones (NTera2-N). The levels of UCH-L1 expression were unaltered in these cell lines following treatment with TNF-alpha, IL-1beta, BDNF, GDNF, dibutyryl cyclic AMP, or phorbol 12-myristate 13-acetate, and remained unchanged by exposure to heat stress. In contrast, its levels were elevated substantially in NTera2 teratocarcinoma cells following retinoic acid-induced neuronal differentiation, accompanied with an increased expression of alpha-synuclein and synaptophysin. These results indicate that UCH-L1 is expressed constitutively in human neual cell lines, where it is upregulated following induction of neuronal differentiation, but unaffected by exposure to heat stress, cytokines, or growth/differentiation factors which are supposed to be invloved in the nigral neuronal death and survival in PD.
Satoh
J I
JI
Division of Neurology, Department of Internal Medicine, Saga Medical School, Saga, Japan. satojl@post.saga-med.ac.jp
Kuroda
Y
Y
D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016631:Lewy Bodies / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D018243:Teratocarcinoma; D013869:Thiolester Hydrolases / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D043222:Ubiquitin Thiolesterase
D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007375:Interleukin-1; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase