The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons

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Merino Martín, José Joaquín and Garcimartín Álvarez, Alba and López-Oliva Muñoz, María Elvira and Benedí González, Juana María and González Burgos, Elena (2016) The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons. International Journal of Molecular Sciences, 17 (12). p. 2005. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms17122005




Abstract

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.


Item Type:Article
Uncontrolled Keywords:AMD3100; CXCR4 chemokine receptor; cortical neurons in vitro; caspase-3/9; apoptosis; cytochrome c/Bcl-2/Bax; mitochondria; cytosol; neuroprotection
Subjects:Medical sciences > Pharmacy > Molecular biology
Medical sciences > Pharmacy > Pharmacology
Medical sciences > Pharmacy > Animal physiology
Medical sciences > Pharmacy > Neurosciences
ID Code:67116
Deposited On:22 Jul 2021 14:22
Last Modified:18 Aug 2021 08:56

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