RT Journal Article
T1 The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons
A1 Merino Martín, José Joaquín
A1 Garcimartín Álvarez, Alba
A1 López-Oliva Muñoz, María Elvira
A1 Benedí González, Juana María
A1 González Burgos, Elena María
AB Background: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro). Methods: For this aim, AMD3100 (200 nM) was added to cortical neurons for 24 h, and several biomarkers like cell viability, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release, caspase-3/9 activity, proteins Bax and Bcl-2 translocation, and cytochrome c release were analyzed by immunoblot. Results: CXCR4 blockade by AMD3100 (200 nM, 24 h) induces mitochondrial hyperpolarization and increases caspase-3/9 hyperpolarization without affecting LDH release as compared to untreated controls. AMD3100 also increases cytochrome c release and promotes Bax translocation to the mitochondria, whereas it raises cytosolic Bcl-2 levels in brain cortical neurons. Conclusion: CXCR4 blockade induces cellular death via intrinsic apoptosis in rat brain cortical neurons in absence of insult.
PB MDPI
SN 1422-0067
YR 2016
FD 2016-11-30
LK https://hdl.handle.net/20.500.14352/19208
UL https://hdl.handle.net/20.500.14352/19208
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Centro de Implantología y Rehabilitación Oral Multidisciplinaria (CIROM)
DS Docta Complutense
RD 11 abr 2025