Modulation of tyrosine hydroxylase expression by melatonin in human SH-SY5Y neuroblastoma cells |
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Authors: | McMillan Catherine R Sharma Rohita Ottenhof Tom Niles Lennard P |
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Affiliation: | Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC-4N77, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. |
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Abstract: | We have previously reported in vivo preservation of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, following treatment with physiological doses of melatonin, in a 6-hydroxydopamine model of Parkinson's disease. Based on these findings, we postulated that melatonin would similarly modulate the expression of TH in vitro. Therefore, using human SH-SY5Y neuroblastoma cells which can differentiate into dopaminergic neurons following treatment with retinoic acid, we first examined whether these cells express melatonin receptors. Subsequently, the physiological dose-dependent effects of melatonin on TH expression were examined in both undifferentiated and differentiated cells. The novel detection of the G protein-coupled melatonin MT(1) receptor in SH-SY5Y cells by RT-PCR was confirmed by sequencing and Western blotting. In addition, following treatment of SH-SY5Y cells with melatonin (0.1-100 nM) for 24h, Western analysis revealed a significant increase in TH protein levels. A biphasic response, with significant increases in TH protein at 0.5 and 1 nM melatonin and a reversal at higher doses was seen in undifferentiated cells; whereas in differentiated cells, melatonin was effective at doses of 1 and 100 nM. These findings suggest a physiological role for melatonin in modulating TH expression, possibly via the MT(1) receptor. |
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Keywords: | Melatonin MT1 receptor mRNA and protein MT2 receptor Tyrosine hydroxylase Cell differentiation Retinoic acid |
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