Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells

TRH (thyroliberin)and its analogues were reported to possess neuroprotective effects in cellular and animal experimental models of acute and chronic neurodegenerative diseases In the present study we evaluated effects of TRH and its three stable analogues montirelin (CG-3703) RGH-2202 and Z-TRH (N-(carbobenzyloxy)-pGlutamyl-Histydyl-Proline) on the neuronally differentiated human neuroblastoma SH-SY5Y cell line which is widely accepted for studying potential neuroprotectants We found that TRH and all the tested analogues at concentrations 0 1-50 mu M attenuated cell damage induced by MPP(+) (2 mM) 3-nitropropionate (10 mM) hydrogen peroxide (0 5 mM) homocysteme (250 mu M) and beta-amyloid (20 mu M) in retinoic acid differentiated SH-SY5Y cells Furthermore we demonstrated that TRH and its analogues decreased the staurosporine (0 5 mu M)-induced LDH release caspase-3 activity and DNA fragmentation which indicate the anti-apoptotic proprieties of these peptides The neuroprotective effects of TRH (10 mu M) and RGH-2202 (10 mu M) on St-induced cell death was attenuated by inhibitors of PI3-K pathway (wortmannin and LY294002) but not MAPK/ERK1/2 (PD98059 and U0126) Moreover TRH and its analogues at neuroprotective concentrations (1 and 10 mu M) increased expression of Bcl-2 protein as confirmed by Western blot analysis All in all these results extend data on neuroprotective properties of TRH and its analogues and provide evidence that mechanism of ann-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3 K/Akt pathway and Bcl-2 Furthermore the data obtained on human cell line with a dopaminergic phenotype suggest potential utility of TRH and its analogues in the treatment of some neurodegenerative diseases including Parkinson s disease (C) 2010 Elsevier Ltd All rights reserved