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Influence of serum concentration in retinoic acid and phorbol ester induced differentiation of SH-SY5Y human neuroblastoma cell line

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Abstract

Numerous protocols to establish dopaminergic phenotype in SH-SY5Y cells have been reported. In most of these protocols there are variations in concentration of serum used. In this paper, we compared the effects of high (10%), low (3%) and descending (2.5%/1%) serum concentration in differentiation medium containing different proportion of retinoic acid (RA) and 12-O-Tetradecanoylphorbol-13-acetate (TPA) or RA-only on the undifferentiated SH-SY5Y cells with regards to cell morphology, biochemical and gene expression alterations. Cells differentiated in culture medium containing low and descending serum concentrations showed increased number of neurite projections and reduced proliferation rates when compared to undifferentiated cells. The SH-SY5Y cells differentiated in culture medium containing 3% RA and low serum or descending (2.5%/1% RA/TPA) were found to be more susceptible to 6-hydroxydopamine (6-OHDA) induced cytotoxicity. Cells differentiated with RA/TPA or RA differentiated showed increased production of the α-synuclein (SNCA) neuroprotein and dopamine neurotransmitter compared to undifferentiated cells, regardless serum concentrations used. There was no significant difference in the expression of tyrosine hydroxylase (TH) gene between undifferentiated and differentiated SH-SY5Y cells. However, the expression of dopamine receptor D2 (DRD2) gene was markedly increased (p<0.05) in differentiated cells with 3% serum and RA only when compared to undifferentiated cells. In conclusion, to terminally differentiate SH-SY5Y cells to be used as a cell-based model to study Parkinson’s disease (PD) to investigate molecular mechanisms and drug discovery, the optimal differentiation medium should contain 3% serum in RA-only

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Abbreviations

RA:

retinoic acid

TPA:

12-O-Tetradecanoylphorbol-13-acetate

SH-SY5Y:

human neuroblastoma cell line

6-OHDA:

6-hydroxydopamine

SNCA:

α-synuclein

TH:

tyrosine hydroxylase

DRD2:

dopamine receptor D2

PD:

Parkinson’s disease

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Acknowledgements

The authors are very grateful to Dr Premdass Ramdas for his helpful guidance and technical assistance in the PCR assays.

Funding

This study was supported by International Medical University, Kuala Lumpur research grant (Grant: IMU R 194 2016).

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Authors and Affiliations

  1. School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia

    Kasthuri Bai Magalingam & Nagaraja Haleagrahara

  2. Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Malaysia, Bandar Sunway, Malaysia

    Ammu Kutty Radhakrishnan

  3. Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia

    Ammu Kutty Radhakrishnan & Sushela Devi Somanath

  4. Department of Pharmaceutics, Faculty of Pharmacy, King Abdul Aziz University, Jeddah, Saudi Arabia

    Shadab Md

  5. College of Public Health, Medicine and Veterinary Sciences, James Cook University, Townsville, Queensland, 4811, Australia

    Nagaraja Haleagrahara

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All authors whose names appear on the submission contributed to the study conception, design of the work, analysis and interpretation of data. All authors read and approved the version to be published.

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Correspondence to Nagaraja Haleagrahara.

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Authors Kasthuri Bai Magalingam, Ammu Kutty Radhakrishnan, Sushela Devi Somanath, Shadab Md, and Nagaraja Haleagrahara declare that we have no conflict of interest.

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This study was approved by the International Medical University, Institutional Research Ethics Committee. This article does not contain any studies with human participants or animals performed by any of the authors

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Magalingam, K.B., Radhakrishnan, A.K., Somanath, S.D. et al. Influence of serum concentration in retinoic acid and phorbol ester induced differentiation of SH-SY5Y human neuroblastoma cell line. Mol Biol Rep 47, 8775–8788 (2020). https://doi.org/10.1007/s11033-020-05925-2

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