The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
APOE and the regulation of microglial nitric oxide production: a link between genetic risk and oxidative stress
Abstract
The mechanism linking the APOE4 gene with increased susceptibility for Alzheimer's disease (AD) and poorer outcomes following closed head injury and stroke is unknown. One potential link is activation of the innate immune system in the CNS. Our previously published data demonstrated that apolipoprotein E regulates production of nitric oxide, a critical cytoactive factor released by immune active macrophages. To determine if immune regulation is different in the presence of apolipoprotein E4 compared to apolipoprotein E3, we have measured NO production by peritoneal and CNS macrophages (microglia) cultured from transgenic mice that only express the human apoE4 or apoE3 protein isoform. Significantly more NO was produced in APOE4 mice compared to APOE3 transgenic mice that only express human apoE3 protein. Similarly, monocyte derived macrophages from humans carrying APOE4 gene alleles also produce significantly greater NO than those individuals with APOE3. The mechanism for this isoform-specific difference in NO production is not known and multiple sites in the NO production pathway may be affected. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein are not significantly different between the APOE3 and APOE4 mice, suggesting that induction of iNOS is not a primary cause of the increased NO production in APOE4 animals. One alternative regulatory mechanism that demonstrates isoform specificity is arginine transport, which is greater in microglia from APOE4 tran…
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“Recently, several studies have shown that APOE4 is associated with increased innate immune reactivity and enhanced cytokine secretion in primary microglia and peripheral macrophages in various animal models as well as human subjects [31–42].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [39]
Citations
Cites
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Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
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Self-citationWhite, F., Nicoll, J. A. R., Roses, A. D., & Horsburgh, K. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0401 · Cited by 128
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Lynch, J. R., Tang, W., Wang, H., Vitek, M. P., Bennett, E. R., Sullivan, P. M., Warner, D. S., & Laskowitz, D. T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306923200 · Cited by 394
Self-citationAPOE genotype-specific differences in the innate immune response
Vitek, M. P., Brown, C. M., & Colton, C. A. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.014 · Cited by 362
Self-citationTzioras, M., Davies, C., Newman, A., Jackson, R., & Spires‐Jones, T. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12529 · Cited by 147
25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
Wong, M. Y., Lewis, M., Doherty, J. J., Shi, Y., Cashikar, A. G., Amelianchik, A., Tymchuk, S., Sullivan, P. M., Qian, M., Covey, D. F., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01869-3 · Cited by 121
Keene, C. D., Cudaback, E., Li, X., Montine, K. S., & Montine, T. J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.08.002 · Cited by 103
Metadata
- Authors
- COLTON, C., BROWN, C., COOK, D., NEEDHAM, L., XU, Q., CZAPIGA, M., SAUNDERS, A., SCHMECHEL, D., RASHEED, K., & VITEK, M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2002-09
- Volume
- 23
- Issue
- 5
- Pages
- 777-785
- ISSN
- 0197-4580
- Cited by
- 108
- References
- 8
- Language
- en
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- The paper
- COLTON, C., BROWN, C., COOK, D., NEEDHAM, L., XU, Q., CZAPIGA, M., SAUNDERS, A., SCHMECHEL, D., RASHEED, K., & VITEK, M. (2002). APOE and the regulation of microglial nitric oxide production: a link between genetic risk and oxidative stress. Neurobiology of Aging. https://doi.org/10.1016/s0197-4580(02)00016-7
