HMG-CoA reductase inhibitor induces a transient activation of high affinity nerve growth factor receptor, trk, and morphological differentiation with fatal outcome in PC12 cells
| Autor: | Takanori Kumano, Masaru Kuriyama, Hiroto Nakagawa, Tatsuro Mutoh |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Simvastatin Neurite Cell Culture Techniques Apoptosis Tropomyosin receptor kinase A Biology PC12 Cells chemistry.chemical_compound Internal medicine medicine Animals Autocrine signalling Molecular Biology Cell Size General Neuroscience Tyrosine phosphorylation Helminth Proteins Cell biology Rats Nerve growth factor Endocrinology nervous system chemistry Cell culture Trk receptor Neurology (clinical) Hydroxymethylglutaryl-CoA Reductase Inhibitors Receptors Transforming Growth Factor beta Developmental Biology medicine.drug |
| Zdroj: | Brain research. 859(1) |
| ISSN: | 0006-8993 |
| Popis: | The present study was aimed at investigating the possible toxicity of simvastatin on a neuronal cell line, PC12 cells. Simvastatin clearly induced a transient morphological differentiation as evidenced by the occurrence of neurite outgrowth with a transient activation of the high affinity nerve growth factor receptor, Trk, but died at 36 h after its addition. Tyrosine autophosphorylation of the Trk protein also disappeared at 36 h after addition. During the morphological differentiation, NGF mRNA expression was upregulated transiently and returned to the basal level at 36 h after addition of simvastatin. These results suggest that simvastatin is neurotoxic and PC12 cells elicited a protective response, involving a transient activation of a Trk-mediated intracellular signal transduction pathway by an autocrine secretion of NGF, although these responses did not persist against pro-apoptotic signals and resulted in an apoptosis of the PC12 cells. |
| Databáze: | OpenAIRE |
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