In the current study, we have evaluated the ability of substance P (SP) and other neurokinin I receptor (NK1) agonists to protect, in a dose-and time-dependent manner, primary cultures of rat cerebellar granule cells (CGCs) from serum and potassium deprivation-induced cell death (S-K5). We also established the presence of SP high affinity NK1 transcripts and the NK1 protein localization in the membrane of a sub-population of CGCs. Moreover, SP significantly and dose-dependently reduced the Akt 1/2 and Erk1/2 dephosphorylation induced by S-K5 conditions, as demonstrated by Western blot analysis. Surprisingly, in SP-treated CGCs caspase-3 activity was not inhibited, while the calpain-1 activity was moderately reduced. Corroborating this result, SP blocked calpain-mediated cleavage of tau protein, as demonstrated by the reduced appearance of a diagnostic fragment of 17 kDa by Western blot analysis. In addition, SP induced a significant reduction of the delayed rectifier K+ currents (I-k) in about 42% of the patched neurons, when these were evoked with depolarizing potential steps. Taken together, the present results demonstrate that the activation of NK1 receptors expressed in CGCs promote the neuronal survival via pathways involving Akt and Erk activation and by inhibition Of Ik which can contribute to the neuroprotective effect of the peptide. (C) 2007 Published by Elsevier Ltd.

Amadoro, G., Pieri, M., Ciotti, M., Carunchio, I., Canu, N., Calissano, P., et al. (2007). Substance P provides neuroprotection in cerebellar granule cells through Akt and MAPK/Erk activation: Evidence for the involvement of the delayed rectifier potassium current. NEUROPHARMACOLOGY, 52(6), 1366-1377 [10.1016/j.neuropharm.2007.01.020].

Substance P provides neuroprotection in cerebellar granule cells through Akt and MAPK/Erk activation: Evidence for the involvement of the delayed rectifier potassium current

PIERI, MASSIMO;CANU, NADIA;CALISSANO, PIETRO;ZONA, CRISTINA;
2007

Abstract

In the current study, we have evaluated the ability of substance P (SP) and other neurokinin I receptor (NK1) agonists to protect, in a dose-and time-dependent manner, primary cultures of rat cerebellar granule cells (CGCs) from serum and potassium deprivation-induced cell death (S-K5). We also established the presence of SP high affinity NK1 transcripts and the NK1 protein localization in the membrane of a sub-population of CGCs. Moreover, SP significantly and dose-dependently reduced the Akt 1/2 and Erk1/2 dephosphorylation induced by S-K5 conditions, as demonstrated by Western blot analysis. Surprisingly, in SP-treated CGCs caspase-3 activity was not inhibited, while the calpain-1 activity was moderately reduced. Corroborating this result, SP blocked calpain-mediated cleavage of tau protein, as demonstrated by the reduced appearance of a diagnostic fragment of 17 kDa by Western blot analysis. In addition, SP induced a significant reduction of the delayed rectifier K+ currents (I-k) in about 42% of the patched neurons, when these were evoked with depolarizing potential steps. Taken together, the present results demonstrate that the activation of NK1 receptors expressed in CGCs promote the neuronal survival via pathways involving Akt and Erk activation and by inhibition Of Ik which can contribute to the neuroprotective effect of the peptide. (C) 2007 Published by Elsevier Ltd.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09
English
Con Impact Factor ISI
Cerebellar granule cells; Neuroprotection; Substance P; Tachykinin receptors
calpain i; caspase 3; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; neurokinin 1 receptor; neurokinin 1 receptor agonist; potassium; protein; protein kinase B; protein kinase B beta; substance P; tau protein; animal cell; article; cell culture; cell death; cell membrane; cell survival; controlled study; enzyme activity; granule cell; nerve cell; neuroprotection; nonhuman; potassium current; priority journal; protein dephosphorylation; protein localization; rat; Western blotting; Animals; Blotting, Western; Calpain; Caspases; Cerebellum; Cytoplasmic Granules; Delayed Rectifier Potassium Channels; Electrophysiology; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Microscopy, Phase-Contrast; Mitogen-Activated Protein Kinases; Neuroprotective Agents; Oncogene Protein v-akt; Patch-Clamp Techniques; Potassium; Rats; Rats, Wistar; Receptors, Neurokinin-1; Reverse Transcriptase Polymerase Chain Reaction; Substance P; Tachykinins
Amadoro, G., Pieri, M., Ciotti, M., Carunchio, I., Canu, N., Calissano, P., et al. (2007). Substance P provides neuroprotection in cerebellar granule cells through Akt and MAPK/Erk activation: Evidence for the involvement of the delayed rectifier potassium current. NEUROPHARMACOLOGY, 52(6), 1366-1377 [10.1016/j.neuropharm.2007.01.020].
Amadoro, G; Pieri, M; Ciotti, M; Carunchio, I; Canu, N; Calissano, P; Zona, C; Severini, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/56804
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