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Somatostatin-Mediated Changes in Microtubule-Associated Proteins and Retinoic Acid–Induced Neurite Outgrowth in SH-SY5Y Cells

  • Seungil Paik
  • Rishi K. Somvanshi
  • Ujendra KumarEmail author
Article

Abstract

Somatostatin (SST) is a growth hormone inhibitory peptide involved in regulation of several physiological responses of cells including neurotransmission, cell migration, maturation, and neurite formation. In the present study, we examined the role of SST in all-trans retinoic acid (RA)–induced progression of neurite outgrowth in SH-SY5Y cells. We also determined the morphological and developmental changes in prominent intracellular markers of neurite growth including microtubule-associated protein 2 (MAP2), neuron-specific III β-tubulin (TUJ1), and Tau. Here, we present evidence that SST is a molecular determinant in regulating the transition of SH-SY5Y cells from non-neuronal entity to neuronal phenotype in response to RA. The results from present study reveal that SST changes the distributional pattern of MAP2/Tau and TUJ1, and activates extracellular signal–regulated kinase (ERK1/2) signaling pathway through SST receptors (SSTRs). The expression of MAP2 and Tau remains elevated upon treatment with RA and SST alone or in combination. Importantly, we identified that the cells displaying strong co-expression of SST and TUJ1 are more likely to bear elongated neurite formation than cells devoid of such expression. These findings show that the site-specific expression of MAP2 and TUJ1 is an essential determinant of neurite outgrowth in SH-SY5Y cells in RA-mediated differentiation. Taken together, results presented here further substantiates the role of SST in the promotion of neurite formation and elongation in SH-SY5Y cells in combination with RA. Investigating how SST can improve neurite formation in neurodegenerative disease may help to develop new therapeutic approach in improving cognitive function and memory loss.

Keywords

Cytoskeleton Neurite outgrowth Neuroblastoma Somatostatin SH-SY5Y MAP2 Tau Cell differentiation 

Abbreviations

Beta-amyloid

AD

Alzheimer’s disease

BDNF

Brain-derived neurotrophic factor

CNS

Central nervous system

CSF

Cerebrospinal fluid

DMEM

Dulbecco’s modified eagle’s medium

ERK

Extracellular signal–regulated kinase

FBS

Fetal bovine serum

hCMEC/D3

Human brain microvascular endothelial cells

HRP

Horseradish peroxidase

HD

Huntington’s disease

MAP2

Microtubule-associated protein 2

MAPK

Mitogen-activated protein kinase

MS

Multiple sclerosis

NGF

Nerve growth factor

NGS

Normal goat serum

PBS

Phosphate-buffered saline

PCNA

Proliferating cell nucleus antigen

RA

Retinoic acid

SDS

Sodium dodecyl sulfate

SH-SY5Y

Human neuroblastoma cells

SST

Somatostatin

SSTR

Somatostatin receptor

RT

Room temperature

TUJ1

βIII tubulin

Notes

Acknowledgments

SP is the recipient of CIHR Doctoral Research Award (GSD 134858) and UBC 4 Year Fellowship.

Funding information

This work was supported by grants from the Canadian Institute of Health Research (MOP 74465) and NSERC (402594-11 and 16-05171) Canada to UK.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. 1.Faculty of Pharmaceutical SciencesUniversity of British ColumbiaVancouverCanada

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