5-HT_2A serotonin receptor agonist DOI alleviates cytotoxicity in neuroblastoma cells: Role of the ERK pathway

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• 作者：Zoya Marinova^a ; ^{Zoya.Marinova@kjpdzh.ch} ; Susanne Walitza^a ; ^b ; Edna Gr&uuml ; nblatt^a ; ^b
• 关键词：ANOVA ; analysis of variance ; CI ; cell index ; DOI ; (± ; )-2 ; 5-dimethoxy-4-iodoamphetamine hydrochloride ; ERK ; extracellular signal-regulated kinase ; FBS ; fetal bovine serum ; 5-HT ; 5-hydroxytryptamine ; MAPK ; mitogen-activated protein kinase ; PKC ; protei
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2013
• 出版时间：1 July, 2013
• 年：2013
• 卷：44
• 期：Complete
• 页码：64-72
• 全文大小：1489 K

文摘

Disturbances of serotonergic signaling, including the serotonin 2A (5-HT_2A) receptor, have been implicated in neuropsychiatric and neurodegenerative disorders. The aim of the present study was to characterize the effect of a 5-HT_2A receptor agonist on cytotoxicity in a neuronal cell line and address the involved mechanism. HTR2A mRNA and protein expression in human neuroblastoma SK-N-SH cells was confirmed. Cells were subjected to serum deprivation and cell viability was monitored continuously with xCELLigence. In a dose-response study the 5-HT_2A agonist (¡À)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (25 nM to 5 ¦ÌM) protected against serum deprivation cytotoxicity. The selective 5-HT_2A receptor antagonist MDL 11,939, the general protein tyrosine kinase inhibitor genistein, and the extracellular signal-regulated kinase (ERK) pathway MEK inhibitor U0126, all attenuated DOI's protective effect. An antibody array suggested that 1 ¦ÌM DOI affected phosphorylation of several tyrosine kinases. Western blot further confirmed that DOI transiently increased ERK phosphorylation, indicating its activation. Finally, protective concentrations of DOI increased cellular mitochondrial mass, an effect prevented by pretreatment with U0126. In conclusion, our results suggest that DOI protects SK-N-SH cells against serum deprivation through ERK pathway activation. They imply 5-HT_2A receptor modulation as a potential target for neuroprotection.