The protective effect of TRH and its analogues on staurosporine-but not doxorubicin-induced apoptosis in primary cortical neurons

• Autorzy: Jantas D. , Jaworska-Feil L. , Lipkowski A.W. , Lason W.
• Języki publikacji: EN

Abstrakty

EN

In the present study we investigated the infl uence of thyrotropinreleasing hormone (TRH, pGlu-His-Pro-NH2) and its more stable analogues: CG-3703 (Montirelin), RGH-2202 (L-6-keto-piperidine-2carbonyl-L-leucyl-L-prolinamide) and Z-TRH (Z-pGlutamyl-Histydyl-Proline) on neuronal apoptosis evoked by staurosporine ñ or doxorubicin, agents activating mitochondrial or extracellular (FAS) apoptotic cell death, respectively. We showed that TRH (0.001ñ10 μM) in U-shape concentration dependent way (effective concentrations: 0.01 and 0.1 μM) partially attenuated the staurosporine (0.5 μM) ñ but not doxorubicin (0.5 μM)-evoked cell damage in mouse 7 DIV cortical neurons only when added 24 h before toxin administration. The TRH analogues (MON, RGH, Z-TRH) were also effective in lower concentration (0.001 μM) than TRH in attenuation of the staurosporine-induced LDH release. Moreover, that benefi cial effect of TRH and its analogues was not accompanied with its infl uence on caspase-3 activity, though the attenuation of number of apoptotic cells was observed in Hoechstís staining. Furthermore, we found that neither PI3-K (wortmannin 10 μM, LY294002 1 μM) nor MAPK/ERK1/2 (PD098059 1 uM and U0126 1 μM) inhibitors were able to abolish protection served by TRH and MON. There was no protection observed when peptides were added concomitantly with staurosporine and doxorubicin. The obtained data showed ameliorating effect of pretreatment with low concentrations of TRH and its analogues on neuronal cell death mediated by agent activating mitochondrial pathway of apoptosis. That effect seems to be caspase-3-independent and does not engage the PI3-K/ Akt and MAPK/ERK1/2 cellular prosurvival pathways. Supported by grant No. 2PO5A15530 from the Ministry of Education and Science (Warsaw, Poland)

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.85

Twórcy

autor

Jantas D.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Jaworska-Feil L.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Lipkowski A.W.

• Department of Neuropeptide, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lason W.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland