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Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells.
Neuropeptides. 2010 Dec; 44(6):495-508.N

Abstract

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 μM attenuated cell damage induced by MPP(+) (2 mM), 3-nitropropionate (10 mM), hydrogen peroxide (0.5 mM), homocysteine (250 μM) and beta-amyloid (20μM) in retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the staurosporine (0.5 μM)-induced LDH release, caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these peptides. The neuroprotective effects of TRH (10 μM) and RGH-2202 (10 μM) 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 μM) 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 anti-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3K/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.

Authors+Show Affiliations

Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20869113

Citation

Jaworska-Feil, L, et al. "Protective Effects of TRH and Its Analogues Against Various Cytotoxic Agents in Retinoic Acid (RA)-differentiated Human Neuroblastoma SH-SY5Y Cells." Neuropeptides, vol. 44, no. 6, 2010, pp. 495-508.
Jaworska-Feil L, Jantas D, Leskiewicz M, et al. Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. Neuropeptides. 2010;44(6):495-508.
Jaworska-Feil, L., Jantas, D., Leskiewicz, M., Budziszewska, B., Kubera, M., Basta-Kaim, A., Lipkowski, A. W., & Lason, W. (2010). Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. Neuropeptides, 44(6), 495-508. https://doi.org/10.1016/j.npep.2010.08.004
Jaworska-Feil L, et al. Protective Effects of TRH and Its Analogues Against Various Cytotoxic Agents in Retinoic Acid (RA)-differentiated Human Neuroblastoma SH-SY5Y Cells. Neuropeptides. 2010;44(6):495-508. PubMed PMID: 20869113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. AU - Jaworska-Feil,L, AU - Jantas,D, AU - Leskiewicz,M, AU - Budziszewska,B, AU - Kubera,M, AU - Basta-Kaim,A, AU - Lipkowski,A W, AU - Lason,W, PY - 2010/05/04/received PY - 2010/08/19/revised PY - 2010/08/30/accepted PY - 2010/9/28/entrez PY - 2010/9/28/pubmed PY - 2011/3/1/medline SP - 495 EP - 508 JF - Neuropeptides JO - Neuropeptides VL - 44 IS - 6 N2 - 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 μM attenuated cell damage induced by MPP(+) (2 mM), 3-nitropropionate (10 mM), hydrogen peroxide (0.5 mM), homocysteine (250 μM) and beta-amyloid (20μM) in retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the staurosporine (0.5 μM)-induced LDH release, caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these peptides. The neuroprotective effects of TRH (10 μM) and RGH-2202 (10 μM) 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 μM) 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 anti-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3K/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. SN - 1532-2785 UR - https://www.unboundmedicine.com/medline/citation/20869113/Protective_effects_of_TRH_and_its_analogues_against_various_cytotoxic_agents_in_retinoic_acid__RA__differentiated_human_neuroblastoma_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4179(10)00087-9 DB - PRIME DP - Unbound Medicine ER -