The C‐terminal domain of the heavy chain of tetanus toxin rescues cerebellar granule neurones from apoptotic death: involvement of phosphatidylinositol 3‐kinase and mitogen‐activated protein kinase pathways

• DOI: 10.1111/j.1471-4159.2004.02586.x
• Publication Date: 2004-08-16T14:44:00Z
• Authors: Imane Chaïb‐Oukadour; Carles Gil; José Aguilera
• Keywords: Wortmannin; MAPK cascade

When cultured cerebellar granule neurones are transferred from a medium containing high extracellular potassium concentration ([K+]e) (25 mm) to one with lower [K+]e (5 mm), caspase-3 activity is induced and cells die apoptotically. In contrast, if in non-depolarizing conditions treated brain-derived neurotrophic factor (BDNF), activity, chromatin condensation cell death markedly diminished. this study, we show that the C-terminal domain of tetanus toxin heavy-chain (Hc-TeTx) able produce same neuroprotective effect, as assessed by reduction tetrazolium salts condensation. Hc-TeTx-conferred neuroprotection appears depend on phosphatidylinositol 3-kinase (PI3K) mitogen-activated protein kinase kinase, demonstrated selective inhibitors Wortmannin PD98059, respectively. Hc-TeTx also induces phosphorylation tyrosine BDNF receptor, activation p21Ras its GTP-bound form, cascade including extracellular-signal-regulated kinases-1/2 (ERK-1/2), p90 ribosomal S6 (p90rsk) CREB (cAMP-response-element-binding protein). On other hand, Akt pathway detected, well inhibition active form caspase-3. These results point an implication both PI3K- ERK-dependent pathways promotion survival Hc-TeTx.