Journal of neurochemistry
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Journal of neurochemistry · Dec 2003
Comparative StudyEnhancement of ischemia-induced tyrosine phosphorylation of Kv1.2 by vascular endothelial growth factor via activation of phosphatidylinositol 3-kinase.
Our studies observed that, consistent with the literature, ischemic/hypoxic insults increased the expression of voltage-gated potassium channel (Kv) 1.2 potassium channel as well as elevating the endogenous level of vascular endothelial growth factor (VEGF) in neurons of adult rat brain following middle cerebral artery occlusion and in SH-SY5Y cells after hypoxia and glucose deprivation. Concomitantly, we also observed that ischemic injury increased the tyrosine phosphorylation of Kv 1.2 in in vivo and in vitro; the introduction of exogenous VEGF could attenuate cell death in in vitro models. ⋯ In substantiation of this result, we used anti-sense methodology to suppress the expression of endogenous VEGF, which significantly inhibited the tyrosine phosphorylation of Kv 1.2 and increased cell death elicited by ischemic/hypoxic injury. Finally, the enhancement of the tyrosine phosphorylation of the channel by VEGF in neuronal cells was significantly attenuated in the presence of wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), or genestin, an inhibitor of tyrosine kinase, thus suggesting that the phosphorylation of Kv 1.2 induced by VEGF is mechanistically linked to the PI3-K pathway.
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Journal of neurochemistry · Dec 2003
Expression of galectin-3 in neuronally differentiating PC12 cells is regulated both via Ras/MAPK-dependent and -independent signalling pathways.
Galectin-3 (gal-3) is a member of the galectin family of lectins whose expression strongly depends on the cellular state. Here we show that in PC12 cells the expression of gal-3 protein is regulated via Ras- and mitogen-activated protein kinase (MAPK)-dependent and independent signalling pathways and correlates with nerve growth factor (NGF)-mediated neuronal differentiation. Gal-3 expression, activation of the MAPK ERK1/2 and neurite outgrowth are induced by NGF and basic fibroblast growth factor (bFGF), but not by ciliary neurotrophic factor (CNTF), epidermal growth factor, insulin or interleukin-6 (IL-6). ⋯ NGF- and staurosporine-induced gal-3-expression is also regulated at the transcriptional level. Our data suggest the presence of complex induction mechanisms of gal-3 expression in neuronally differentiating PC12 cells involving NGF-, but not CNTF- and IL-6-driven (in NGF-primed cells) Ras/MAPK-related signalling pathways. Staurosporine, in contrast, induces gal-3 expression by a Ras/MAPK-independent mechanism.