Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

Abstract

Secretory phospholipase A₂ (sPLA₂) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA₂ (sPLA₂-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA₂ is itself released, and a possible relation between glutamate receptors and sPLA₂ exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA₂-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA₂-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA₂-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA₂-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA₂-IIA secretion. Moreover, KA-induced sPLA₂-IIA secretion is dependent on Ca²⁺ and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA₂ secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.

Apelin inhibits adipogenesis and lipolysis through distinct molecular pathways

“…Just like the vesicular exocytosis in other endocrine cells (Zhang et al, 2009;Than et al, 2011b), secretion of adipokines are highly regulated (Than et al, 2011a(Than et al, , 2012. And these adipokines regulate metabolism in peripheral tissues and influence the secretion and functions of other metabolic factors (Ouchi et al, 2011;Than et al, 2011a).…”

Slow Excitotoxicity in Alzheimer's Disease

“…Expression of sPLA 2 -IIA is induced by oxidative stress and proinflammatory cytokines [170], and increased sPLA 2 activity is detected in the hippocampus after KA injury [171]. sPLA2-IIA is packaged in fusion-competent vesicles and released in a regulated manner after KA receptor stimulation [172]. The enzyme itself induces exocytosis and neurotransmitter release in neuroendocrine cells and neurons [173].…”

Inhibitors of Lipoxygenase and Cyclooxygenase-2 Attenuate Trimethyltin-Induced Neurotoxicity through Regulating Oxidative Stress and Pro-Inflammatory Cytokines in Human Neuroblastoma SH-SY5Y Cells

“…TMT leads to the breakdown of homeostasis of intracellular calcium concentration via internal stores, such as the mitochondria and endoplasmic reticulum (ER) in human neuroblastoma SH-SY5Y cells [ 10 ]. Excitatory glutamate receptors such as N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/KA) receptors are distributed in SH-SY5Y cells [ 11 , 12 , 13 ]. TMT treatment has been shown to result in neuronal necrosis; the anti-inflammatory agent dexamethasone failed to inhibit neuronal damage in the mouse hippocampus [ 14 ].…”