Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism - PubMed (original) (raw)
. 2000 Mar 17;275(11):7918-24.
doi: 10.1074/jbc.275.11.7918.
Affiliations
- PMID: 10713108
- DOI: 10.1074/jbc.275.11.7918
Free article
Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism
K T Akama et al. J Biol Chem. 2000.
Free article
Abstract
In Alzheimer's disease, beta-amyloid (Abeta) plaques are surrounded by activated astrocytes and microglia. A growing body of evidence suggests that these activated glia contribute to neurotoxicity through the induction of inflammatory cytokines such as interleukin (IL)-1beta and tumor necrosis factor-alpha (TNFalpha) and the production of neurotoxic free radicals, mediated in part by the expression of inducible nitric-oxide synthase (iNOS). Here, we address the possibility that Abeta-stimulated iNOS expression might result from an initial induction of IL-1beta and TNFalpha. We find that in Abeta-stimulated astrocyte cultures, IL-1beta and TNFalpha production occur before iNOS production, new protein synthesis is required for increased iNOS mRNA levels, and the IL-1 receptor antagonist IL-1ra can inhibit nitrite accumulation. Likewise, dominant-negative mutants of tumor necrosis factor-alpha receptor-associated factor (TRAF) 6, TRAF2, and NFkappaB-inducing kinase (NIK), intracellular proteins involved in IL-1 and TNFalpha receptor signaling cascades, inhibit Abeta-stimulated iNOS promoter activity. Our data suggest that Abeta stimulation of astrocyte iNOS is mediated in part by IL-1beta and TNFalpha, and involves a TRAF6-, TRAF2-, and NIK-dependent signaling mechanism.
Similar articles
- Regulation of inducible nitric oxide synthase in proinflammatory cytokine-stimulated human primary astrocytes.
Jana M, Anderson JA, Saha RN, Liu X, Pahan K. Jana M, et al. Free Radic Biol Med. 2005 Mar 1;38(5):655-64. doi: 10.1016/j.freeradbiomed.2004.11.021. Free Radic Biol Med. 2005. PMID: 15683721 - Amyloid-beta peptide enhances tumor necrosis factor-alpha-induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes.
Zeng C, Lee JT, Chen H, Chen S, Hsu CY, Xu J. Zeng C, et al. J Neurochem. 2005 Aug;94(3):703-12. doi: 10.1111/j.1471-4159.2005.03217.x. J Neurochem. 2005. PMID: 16033420 - Amyloid-beta peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release.
Hu J, Akama KT, Krafft GA, Chromy BA, Van Eldik LJ. Hu J, et al. Brain Res. 1998 Mar 2;785(2):195-206. doi: 10.1016/s0006-8993(97)01318-8. Brain Res. 1998. PMID: 9518610 - Fibrillar beta-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo.
Weldon DT, Rogers SD, Ghilardi JR, Finke MP, Cleary JP, O'Hare E, Esler WP, Maggio JE, Mantyh PW. Weldon DT, et al. J Neurosci. 1998 Mar 15;18(6):2161-73. doi: 10.1523/JNEUROSCI.18-06-02161.1998. J Neurosci. 1998. PMID: 9482801 Free PMC article. Review. - Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia.
Hall DT, Ma JF, Marco SD, Gallouzi IE. Hall DT, et al. Aging (Albany NY). 2011 Aug;3(8):702-15. doi: 10.18632/aging.100358. Aging (Albany NY). 2011. PMID: 21832306 Free PMC article. Review.
Cited by
- Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer's disease.
Madhu LN, Kodali M, Upadhya R, Rao S, Somayaji Y, Attaluri S, Shuai B, Kirmani M, Gupta S, Maness N, Rao X, Cai JJ, Shetty AK. Madhu LN, et al. J Extracell Vesicles. 2024 Nov;13(11):e12519. doi: 10.1002/jev2.12519. J Extracell Vesicles. 2024. PMID: 39499013 Free PMC article. - Modeling Alzheimer's disease using human cell derived brain organoids and 3D models.
Fernandes S, Revanna J, Pratt J, Hayes N, Marchetto MC, Gage FH. Fernandes S, et al. Front Neurosci. 2024 Aug 1;18:1434945. doi: 10.3389/fnins.2024.1434945. eCollection 2024. Front Neurosci. 2024. PMID: 39156632 Free PMC article. Review. - Zinc Oxide Nanoparticles Attenuated Neurochemical and Histopathological Alterations Associated with Aluminium Chloride Intoxication in Rats.
Attia FM, Kassab RB, Ahmed-Farid OA, Abdel Moneim AE, El-Yamany NA. Attia FM, et al. Biol Trace Elem Res. 2024 Jul 4. doi: 10.1007/s12011-024-04292-4. Online ahead of print. Biol Trace Elem Res. 2024. PMID: 38963645 - Polar lipids modify Alzheimer's Disease pathology by reducing astrocyte pro-inflammatory signaling through platelet-activating factor receptor (PTAFR) modulation.
Hans S, Stanton JE, Sauer AK, Shiels K, Saha SK, Lordan R, Tsoupras A, Zabetakis I, Grabrucker AM. Hans S, et al. Lipids Health Dis. 2024 Apr 20;23(1):113. doi: 10.1186/s12944-024-02106-z. Lipids Health Dis. 2024. PMID: 38643113 Free PMC article. - Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation.
Müller L, Di Benedetto S. Müller L, et al. Front Immunol. 2024 Apr 4;15:1393324. doi: 10.3389/fimmu.2024.1393324. eCollection 2024. Front Immunol. 2024. PMID: 38638424 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous