In vitro assessment of protamine toxicity with neural cells, its therapeutic potential to counter chondroitin sulfate mediated neuron inhibition, and its effects on reactive astrocytes.

Autor: Nelson DW; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Funnell JL; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Cheung CH; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Quinones GB; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biological Sciences, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Mendoza CS; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biological Sciences, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Bentley M; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biological Sciences, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States., Gilbert RJ; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15 St. Troy, New York 12180, United States; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St. Troy, NY, 12180, United States; Albany Stratton Veteran Affairs Medical Center, 113 Holland Ave. Albany, New York 12208, United States.
Jazyk: angličtina
Zdroj: Advanced therapeutics [Adv Ther (Weinh)] 2024 Feb; Vol. 7 (2). Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1002/adtp.202300242
Abstrakt: Multiple therapies have been studied to ameliorate the neuroinhibitory cues present after traumatic injury to the central nervous system. Two previous in vitro studies have demonstrated the efficacy of the FDA-approved cardiovascular therapeutic, protamine (PRM), to overcome neuroinhibitory cues presented by chondroitin sulfates; however, the effect of a wide range of PRM concentrations on neuronal and glial cells has not been evaluated. In this study, we investigate the therapeutic efficacy of PRM with primary cortical neurons, hippocampal neurons, mixed glial cultures, and astrocyte cultures. We show the threshold for PRM toxicity to be at or above 10 μg/ml depending on the cell population, that 10 μg/ml PRM enables neurons to overcome the inhibitory cues presented by chondroitin sulfate type A, and that soluble PRM allows neurons to more effectively overcome inhibition compared to a PRM coating. We also assessed changes in gene expression of reactive astrocytes with soluble PRM and determined that PRM does not increase their neurotoxic phenotype and that PRM may reduce brevican production and serpin transcription in cortical and spinal cord astrocytes. This is the first study to thoroughly assess the toxicity threshold of PRM with neural cells and study astrocyte response after acute exposure to PRM in vitro.
Databáze: MEDLINE
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