Please use this identifier to cite or link to this item: http://hdl.handle.net/10662/7383
Title: The critical role of lipid rafts nanodomains in the cross-talk between calcium and reactive oxygen and nitrogen species in cerebellar granule neurons apoptosis by extracellular potassium deprivation
Authors: Gutiérrez Merino, Carlos
Silva, Dorinda Marques da
Fortalezas, Sofia Isabel Almeida
Samhan Arias, Alejandro Khaul
Universidad de Extremadura. Departamento de Bioquímica, Biología Molecular y Genética
Keywords: Apoptosis
Neuronas granulares de cerebelo
Calcio citosólico
Especies reactivas de oxígeno y nitrógeno
Balsas de lípidos
Canales de calcio de tipo L
Citocromo b5 reductasa
nNOS
CaMKII " y otras balsas de lípidos proteínas quinasas asociadas
Cerebellar granule neurons
Cytosolic calcium
Reactive oxygen and nitrogen species
Lipid rafts
L-type calcium channels
Cytochrome b5 reductase
CaMKII and other lipid rafts-associated protein kinases
Issue Date: 2016
Publisher: AIMS
Abstract: The apoptosis of cerebellar granule neurons (CGN) induced by low-potassium in serum free medium in vitro has become a widely used model for neuronal apoptosis during in vivo brain development. In this review we shall summarize first the basic features of this model for neuronal apoptosis. Next, we shall focus on the L-type calcium channels (LTCC) inactivation as the primary pro-apoptotic signal in low K+-induced CGN death. This apoptotic process can be split into two major and sequential cellular signaling phases: one reversible phase that offers a temporal window for therapeutic interventions to prevent neuronal death, and an irreversible later phase. Therefore, we shall comment next the critical role of reactive oxygen species (ROS) production and major ROS sources triggering the entry of CGN in the irreversible stages of low K+-induced apoptosis. Then, we shall present the experimental evidences showing clustering of LTCC and ROS producing enzymes in plasma membrane lipid rafts of CGN matured in vitro, which have opened new perspectives for cell signaling in the early and reversible phase of this apoptosis. The role of lipid rafts nanodomains as fast response calcium/nitric oxide transducers of the switch of CGN to low K+ medium will be discussed next. The two major conclusions drawn from this review are: (1) deregulation of the pool of cytochrome b5 reductase associated to plasma membrane-lipid rafts, at least in part due to overexpression of cytochrome b5, can account for the critical superoxide anion overshot which triggers the entry in the irreversible phase of low K+ apoptosis of CGN, and (2) LTCC inactivation is rapidly transduced by lipid rafts nanodomains into a large drop of cytosolic calcium, a switch-off of nitric oxide production and subsequent inactivation of survival signaling pathways dependent on the activity of CaMKII, PKA and Akt/PKB kinases.
URI: http://hdl.handle.net/10662/7383
ISSN: 2372-028X
Appears in Collections:DBYBM - Artículos

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