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Human angiogenin presents neuroprotective and migration effects in neuroblastoma cells

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Abstract

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.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

ANG:

Angiogenin

ERK1/2:

Extracellular regulated kinase1/2

FBS:

Fetal bovine serum

GFP:

Green fluorescent protein

HUVEC:

Human umbilical vein endothelial cell

mANG:

Variant K40I ANG gene

SOD1:

Cu/Zn-superoxide dismutase gene

wANG:

Wild type ANG gene

MTT:

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

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Acknowledgments

This work was supported by the cluster research fund of Hanyang University (HY-2009-C).

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Authors and Affiliations

  1. Department of Neurology, College of Medicine, Hanyang University, #17 Haengdang-dong, Seongdong-gu, Seoul, 139-791, Korea

    Goang-Won Cho, Byung Yong Kang & Seung Hyun Kim

  2. Institute of Biomedical Science, Hanyang University, Seoul, 139-791, Korea

    Goang-Won Cho

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  1. Goang-Won Cho
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Correspondence to Seung Hyun Kim.

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Cho, GW., Kang, B.Y. & Kim, S.H. Human angiogenin presents neuroprotective and migration effects in neuroblastoma cells. Mol Cell Biochem 340, 133–141 (2010). https://doi.org/10.1007/s11010-010-0410-0

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