Staurosporine induces neurite outgrowth in neuronal hybrids (PC12EN) lacking NGF receptors

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). In addition, in NGF-treated PC12 cells, gal-3 expression, ERK1/2 activation and neurite outgrowth could be specifically inhibited at the level of TrkA, Ras and MAPK-kinase, whereas expression of an oncogenic form of Ras leads to gal-3 expression and neurite outgrowth in the absence of growth factors. In NGF-primed PC12 cells, subsequent treatment with CNTF or IL-6 induces ERK1/2 activation and neurite outgrowth, but not gal-3 expression. Treatment of PC12 cells with staurosporine induces gal-3 expression and neurite outgrowth without ERK1/2 activation. NGF-and staurosporineinduced 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. Keywords: ERK, galectin-3, interleukin-6, nerve growth factor, PC12 cells, Ras. Galectin-3 (gal-3) belongs to the galectin family of soluble lectins as defined by (i) amino acid sequence homology and (ii) their affinitiy to b-galactosidic carbohydrate structures (reviewed by Cooper 2002). Dependent on the cell type, gal-3 can be expressed intracellularly (cytoplasm and nucleus) and/or extracellularly (plasma membrane or extracellular space). The expression of gal-3 has been associated with a number of different normal biological and pathological processes, such as apoptotic cell death, differentiation, growth and transformation (reviewed by Rabinovich 1999). Thus, gal-3 expression generally correlates with alterations in the state of cell activation. In this context, a basic question concerns the mechanisms of regulation of gal-3 expression in different cell types (reviewed by Chiariotti et al. 1999). First investigated in mouse and human fibroblasts, the expression of gal-3, which is low or absent in quiescent growth-arrested cells, has been found to be induced after serum addition (reviewed by Kadrofske et al. 1998). In activated Schwann and microglial Received March 13, 2002; revised manuscript received July 2, 2003; accepted August 6, 2003. Address correspondence and reprint requests to Rainer Probstmeier, Neuro-and Tumor Cell Biology Group, Department of Nuclear Medicine, University of Bonn, Sigmund Freud Str. 25, 53105 Bonn, Germany. E-mai...

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“…1994). None of these treatments leads to an activation of ERK1/2 in PC12 cells (Rasouly et al . 1996; the present study).…”

Section: Discussionmentioning

confidence: 99%

Expression of galectin‐3 in neuronally differentiating PC12 cells is regulated both via Ras/MAPK‐dependent and –independent signalling pathways

Kuklinski

Vladimirova²,

Waha

et al. 2003

Journal of Neurochemistry

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“…differentiation in neuronal cells (Frassetto et al, 2006). It can induce neuronal differentiation by neurite outgrowth in PC12 cells (Rasouly et al, 1996;Das et al, 2004). In the present investigation, it was used as a biological inducer of neurite elongation.…”

Section: Discussionmentioning

confidence: 82%

Effect of Pentoxifylline on Staurosporine-Induced Neurite Elongation in PC12 Cells

Diojan

Zhaleh

Azadbakht

et al. 2019

Asian Pac J Cancer Prev

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Objective: Pentoxifylline enhances neurite elongation in PC12 cells. This study investigated the effects of pentoxifylline on staurosporine-induced neurite elongation in PC12 cells. Materials and Methods: There were five treatment groups, including treatment group I (1 nM), treatment group II (10 nM), treatment group III (100 nM), treatment group IV (1uM), and treatment group V (10 mM of pentoxifylline), together with 214 nM staurosporine for a range of time (6, 12 and 24 hours). Cells only treated with staurosporine at a concentration of 214 nM were used as the control group. Cell proliferation, cell death, immunocytochemistry assay, and Total Neurite Length were assessed. Results: The results showed that pentoxifylline increased cell viability (p<0.05) in a dose-and time-dependent manner, and cell death assay showed that cell death decreased in a dose-and time-dependent manner (p<0.05). TNL increased significantly compared with control cells (p<0.05). Immunocytochemistry assay showed that pentoxifylline at low and high concentrations enhanced β-tubulin III and GFAP protein expression compared with control cells. Conclusion: It can be concluded that pentoxifylline has positive effects on the staurosporine-induced neurite outgrowth process in PC12 cells.

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“…PC 12 cells co-cultured with adrenal medullary endothelial cells redifferentiate toward a chromaffin cell-like phenotype with reduced proliferation [40]. On the other hand, hybrid cells obtained by somatic fusion of PC 12 cells with adrenal medullary endothelial cells exhibit an enhanced rate of proliferation, which has been attributed to the constitutive release of autocrine growth factors that accelerate proliferation of these cells [41]. Because tumors grew in all animals, the adrenal environment seems to be permissive or even supportive for intraadrenal PC 12 cell proliferation due to paracrine action of growth factors released from chromaffin and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of Orthotopic Rat Adrenomedullary Neoplasia by Intraadrenal Pheochromocytoma Cell Transplantation

et al. 2001

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We aimed to establish a technically feasible, easily reproducible model of orthotopic adrenomedullary neoplasia. Male rats received adrenal injection of rat pheochromocytoma cells infected with the Escherichia coli gene for beta-galactosidase (lac Z). Each of 10 animals was perfused 7 or 24 days after tumor cell injection; 5 animals of each group were injected with cyclosporin. Animals without tumor cell injection served as controls. Tumor cells were identified and characterized in frozen sections by histochemical and immunohistochemical methods. Immunosuppressed animals had enlarged adrenals 7 days after tumor cell injection. In the rats without immunosuppression the adrenals seemed unaltered despite microscopic demonstration of tumor cells. After 24 days tumors had developed in all animals, weighing 50 times more than normal adrenals in animals with immunosuppression, and 9 times more in animals without immunosuppression. Intraadrenal catecholaminergic tumor cells could be identified by beta-galactosidase expression. No animal showed systemic spread. Generation of adrenomedullary neoplasia by intraadrenal pheochromocytoma cell transplantation is easily reproducible and technically feasible. This model allows simultaneous study of neoplastic and normal adrenal tissues (e.g., regarding their response to drugs intended for diagnostic and therapeutic purposes). The decreased tumor growth in animals without immunosuppression is presumably due to the high number of intraadrenal immunocompetent cells.

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Staurosporine induces neurite outgrowth in neuronal hybrids (PC12EN) lacking NGF receptors

Cited by 21 publications

References 47 publications

Expression of galectin‐3 in neuronally differentiating PC12 cells is regulated both via Ras/MAPK‐dependent and –independent signalling pathways

Expression of galectin‐3 in neuronally differentiating PC12 cells is regulated both via Ras/MAPK‐dependent and –independent signalling pathways

Effect of Pentoxifylline on Staurosporine-Induced Neurite Elongation in PC12 Cells

Induction of Orthotopic Rat Adrenomedullary Neoplasia by Intraadrenal Pheochromocytoma Cell Transplantation

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