Agonist Stimulation of the Serotonin1A Receptor Causes Suppression of Anoxia-Induced Apoptosis via Mitogen-Activated Protein Kinase in Neuronal HN2-5 Cells

Autor: Yasir El-Sherif, Nicholas J. Penington, Tatyana Adayev, Probal Banerjee, Madhabi Barua
Rok vydání: 2001
Předmět:
Agonist
MAPK/ERK pathway
medicine.medical_specialty
Patch-Clamp Techniques
Pyridines
medicine.drug_class
Inositol Phosphates
Excitotoxicity
Apoptosis
Stimulation
Cysteine Proteinase Inhibitors
Biology
medicine.disease_cause
Pertussis toxin
Hippocampus
Biochemistry
Piperazines
Wortmannin
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Internal medicine
In Situ Nick-End Labeling
medicine
Animals
Enzyme Inhibitors
Hypoxia
Protein kinase A
Receptor
Flavonoids
Neurons
8-Hydroxy-2-(di-n-propylamino)tetralin
Enzyme Precursors
Caspase 3
Membrane Proteins
Serotonin Receptor Agonists
Cell biology
Androstadienes
Enzyme Activation
Endocrinology
chemistry
Caspases
Receptors
Serotonin
Calcium-Calmodulin-Dependent Protein Kinases
Calcium
Serotonin Antagonists
Oligopeptides
Receptors
Serotonin
5-HT1
Zdroj: Journal of Neurochemistry. 72:1489-1496
ISSN: 0022-3042
DOI: 10.1046/j.1471-4159.1999.721489.x
Popis: Previous studies have indicated that stimulation of neuronal inhibitory receptors, such as the serotonin 1A receptor (5-HT 1A -R), could cause attenuation of the activity of both N-type Ca 2+ channels and N-methyl-D-aspartic acid receptors, thus resulting in protection of neurons against excitotoxicity. The purpose of this study was to investigate if the 5-HT 1A -R is also coupled to an alternative pathway that culminates in suppression of apoptosis even in cells that are deficient in Ca 2+ channels. Using a hippocampal neuron-derived cell line (HN2-5) that is Ca 2+ channel-deficient, we demonstrate here that an alternative pathway is responsible for 5-HT 1A -R-mediated protection of these cells from anoxia-triggered apoptosis, assessed by deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL). The 5-HT 1A -R agonist-evoked protection was eliminated in the presence of pertussis toxin and also required phosphorylation-mediated activation of mitogen-activated protein kinase (MAPK), as evidenced by the elimination of the agonist-elicited rescue of neuronal cells by the MAPK kinase inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (Pl-3K) inhibitor wortmannin. Furthermore, agonist stimulation of the 5-HT 1A -R caused a 60% inhibition of anoxia-stimulated caspase 3-like activity in the HN2-5 cells, and this inhibition was abrogated by PD98059 but not by wortmannin. Although agonist stimulation of the 5-HT 1A -R caused an activation of PI-3Kγ in HN2-5 cells, out results showed that this PI-3Kγ activity was not linked to the 5-HT 1A -R-promoted regulation of caspase activity and suppression of apoptosis. Thus, in the neuronal HN2-5 cells, agonist binding to the 5-HT 1A -R results in MAPK-mediated inhibition of a caspase 3-like enzyme and a 60-70% suppression of anoxia-induced apoptosis through a Ca 2 + channel-independent pathway.
Databáze: OpenAIRE
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