Molecular and Cellular Biochemistry

, Volume 340, Issue 1–2, pp 133–141

Human angiogenin presents neuroprotective and migration effects in neuroblastoma cells



Human angiogenin (ANG) has been highlighted as an angiogenic factor which supports primary and metastatic tumor growth. Recent genetic studies have shown that ANG is presented as a susceptibility gene for amyotrophic lateral sclerosis (ALS) and ALS-frontotemporal dementia (ALS-FTD). They found several missense mutations, including K40I, which present the weakest functional activity in ANG variants. In this study, we investigate whether human wild type ANG (wANG) and its variant K40I (mANG) maintain their divergent functional capacities in neuronal cells. To evaluate this, SH-SY5Y neuroblastoma cells were transfected with wANG and mANG DNA and identified both wild and mutant ANG are localized to nuclei and have no effects on proliferation. We have shown that human wANG prevented cell death under H2O2-induced oxidative stress in both SH-SY5Y and NSC-34 cells, tested by MTT assay. These effects were more enhanced in motor neuron cell NSC-34. wANG also played a role in cell migration, while mANG decreased these functional activities. Immunoblot analysis revealed that the intracellular signaling of ERK1/2 (at Thr183/Tyr185) was increased following transfection of the wANG gene, and significantly decreased by mANG in neuronal cells. These findings suggest that human ANG plays a critical role in cell protection and migration following alterations in ERK1/2 signaling in SH-SY5Y cells. This may provide the possible relationship between mutations in hANG and other neurodegenerative diseases as well as ALS.


ANG variant K40I ALS Oxidative stress 



Amyotrophic lateral sclerosis




Extracellular regulated kinase1/2


Fetal bovine serum


Green fluorescent protein


Human umbilical vein endothelial cell


Variant K40I ANG gene


Cu/Zn-superoxide dismutase gene


Wild type ANG gene


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Goang-Won Cho
    • 1
    • 2
  • Byung Yong Kang
    • 1
  • Seung Hyun Kim
    • 1
  1. 1.Department of Neurology, College of MedicineHanyang UniversitySeoulKorea
  2. 2.Institute of Biomedical ScienceHanyang UniversitySeoulKorea

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