Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line
Research has found that genes specific to microglia are among the strongest risk factors for Alzheimer’s disease (AD) and that microglia are critically involved in the etiology of AD. Thus, microglia are an important therapeutic target for novel approaches to the treatment of AD. High-throughput in...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10396 |
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| author | Oscar M. Muñoz Herrera Brian V. Hong Ulises Ruiz Mendiola Izumi Maezawa Lee-Way Jin Carlito B. Lebrilla Danielle J. Harvey Angela M. Zivkovic |
| author_facet | Oscar M. Muñoz Herrera Brian V. Hong Ulises Ruiz Mendiola Izumi Maezawa Lee-Way Jin Carlito B. Lebrilla Danielle J. Harvey Angela M. Zivkovic |
| author_sort | Oscar M. Muñoz Herrera |
| collection | DOAJ |
| description | Research has found that genes specific to microglia are among the strongest risk factors for Alzheimer’s disease (AD) and that microglia are critically involved in the etiology of AD. Thus, microglia are an important therapeutic target for novel approaches to the treatment of AD. High-throughput in vitro models to screen molecules for their effectiveness in reversing the pathogenic, pro-inflammatory microglia phenotype are needed. In this study, we used a multi-stimulant approach to test the usefulness of the human microglia cell 3 (HMC3) cell line, immortalized from a human fetal brain-derived primary microglia culture, in duplicating critical aspects of the dysfunctional microglia phenotype. HMC3 microglia were treated with cholesterol (Chol), amyloid beta oligomers (AβO), lipopolysaccharide (LPS), and fructose individually and in combination. HMC3 microglia demonstrated changes in morphology consistent with activation when treated with the combination of Chol + AβO + fructose + LPS. Multiple treatments increased the cellular content of Chol and cholesteryl esters (CE), but only the combination treatment of Chol + AβO + fructose + LPS increased mitochondrial Chol content. Microglia treated with combinations containing Chol + AβO had lower apolipoprotein E (ApoE) secretion, with the combination of Chol + AβO + fructose + LPS having the strongest effect. Combination treatment with Chol + AβO + fructose + LPS also induced APOE and TNF-α expression, reduced ATP production, increased reactive oxygen species (ROS) concentration, and reduced phagocytosis events. These findings suggest that HMC3 microglia treated with the combination of Chol + AβO + fructose + LPS may be a useful high-throughput screening model amenable to testing on 96-well plates to test potential therapeutics to improve microglial function in the context of AD. |
| first_indexed | 2024-03-11T02:20:16Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:20:16Z |
| publishDate | 2023-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-470e8853b5e348d4b4958405a61020b92023-11-18T10:52:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121039610.3390/ijms241210396Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell LineOscar M. Muñoz Herrera0Brian V. Hong1Ulises Ruiz Mendiola2Izumi Maezawa3Lee-Way Jin4Carlito B. Lebrilla5Danielle J. Harvey6Angela M. Zivkovic7Department of Nutrition, University of California, Davis, CA 95616, USADepartment of Nutrition, University of California, Davis, CA 95616, USADepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USADepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USADepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USADepartment of Chemistry, University of California, Davis, CA 95616, USADepartment of Public Health Sciences, University of California, Davis, CA 95616, USADepartment of Nutrition, University of California, Davis, CA 95616, USAResearch has found that genes specific to microglia are among the strongest risk factors for Alzheimer’s disease (AD) and that microglia are critically involved in the etiology of AD. Thus, microglia are an important therapeutic target for novel approaches to the treatment of AD. High-throughput in vitro models to screen molecules for their effectiveness in reversing the pathogenic, pro-inflammatory microglia phenotype are needed. In this study, we used a multi-stimulant approach to test the usefulness of the human microglia cell 3 (HMC3) cell line, immortalized from a human fetal brain-derived primary microglia culture, in duplicating critical aspects of the dysfunctional microglia phenotype. HMC3 microglia were treated with cholesterol (Chol), amyloid beta oligomers (AβO), lipopolysaccharide (LPS), and fructose individually and in combination. HMC3 microglia demonstrated changes in morphology consistent with activation when treated with the combination of Chol + AβO + fructose + LPS. Multiple treatments increased the cellular content of Chol and cholesteryl esters (CE), but only the combination treatment of Chol + AβO + fructose + LPS increased mitochondrial Chol content. Microglia treated with combinations containing Chol + AβO had lower apolipoprotein E (ApoE) secretion, with the combination of Chol + AβO + fructose + LPS having the strongest effect. Combination treatment with Chol + AβO + fructose + LPS also induced APOE and TNF-α expression, reduced ATP production, increased reactive oxygen species (ROS) concentration, and reduced phagocytosis events. These findings suggest that HMC3 microglia treated with the combination of Chol + AβO + fructose + LPS may be a useful high-throughput screening model amenable to testing on 96-well plates to test potential therapeutics to improve microglial function in the context of AD.https://www.mdpi.com/1422-0067/24/12/10396microgliacholesterolAlzheimer’s disease |
| spellingShingle | Oscar M. Muñoz Herrera Brian V. Hong Ulises Ruiz Mendiola Izumi Maezawa Lee-Way Jin Carlito B. Lebrilla Danielle J. Harvey Angela M. Zivkovic Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line International Journal of Molecular Sciences microglia cholesterol Alzheimer’s disease |
| title | Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line |
| title_full | Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line |
| title_fullStr | Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line |
| title_full_unstemmed | Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line |
| title_short | Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line |
| title_sort | cholesterol amyloid beta fructose and lps influence ros and atp concentrations and the phagocytic capacity of hmc3 human microglia cell line |
| topic | microglia cholesterol Alzheimer’s disease |
| url | https://www.mdpi.com/1422-0067/24/12/10396 |
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