L‐lactate Increases Apoptosis in Dopaminergic‐Like PC12 Cells

Abstract

Lactate has been shown to be excitatory through activation of ligand gated calcium channels. Studies have demonstrated that extracellular lactate is capable of activating N‐methyl‐D‐aspartate receptors (NMDAR), acidifying neurons and glial cells, which may contribute to excitotoxicity. Since cerebrospinal fluid (CSF) lactate concentrations are elevated in several neurodegenerative disorders, including Parkinson's disease, we tested the hypothesis that increased L‐lactate may be a contributing factor to excitotoxicity of dopaminergic like PC12 cells. Nerve growth factor derived PC12 cells were exposed to increasing concentrations of L‐lactate (0mM, 1.5mM, 2mM, 3mM, 4mM and 8mM) for 4 hrs which increased cell death in a dose dependent manner, analyzed via flow cytometry using propidium iodide (PI) exclusion. The (EC) 50 value was found to be 3.30 mM. The percent of cells staining positive for PI were significantly increased (P < 0.05): control, 0 mM L‐lactate, 15.0 +/− 0.5 % (n=4) and 4 mM L–lactate, 31.6 +/− 4.6% (n=4). This data suggests that elevated CSF lactate may be a contributing factor to dopaminergic cell death in Parkinson's disease.Support or Funding InformationFunding support: AHA 16PRE27780121, Andrew Chapp, R15‐HL129213, Zhiying Shan; R15‐HL122952, Qing‐Hui Chen. Michigan Technological University Undergraduate Research Internship Program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.