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

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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.

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Abbreviations

Aβ:

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

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Acknowledgments

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

Funding

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.

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  1. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

    Seungil Paik, Rishi K. Somvanshi & Ujendra Kumar

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  1. Seungil Paik
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  2. Rishi K. Somvanshi
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Correspondence to Ujendra Kumar.

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Paik, S., Somvanshi, R.K. & Kumar, U. Somatostatin-Mediated Changes in Microtubule-Associated Proteins and Retinoic Acid–Induced Neurite Outgrowth in SH-SY5Y Cells. J Mol Neurosci 68, 120–134 (2019). https://doi.org/10.1007/s12031-019-01291-2

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