Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMA(III)) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.
Uresti-Rivera, E E
Torres-Ramos, M A
Gandolfi, A J
AffiliationUniv Arizona, Coll Pharm, Dept Pharmacol & Toxicol
MetadataShow full item record
CitationCortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMA(III)) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression. 2016, 41 (10):2559-2572 Neurochem. Res.
Rights© Springer Science+Business Media New York 2016
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractLong-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA(III)), which accumulates in glial cells without compromising cell viability. MMA(III) LD50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA(III) concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA(III) concentrations that also induced TNF-α over-expression. Other effects of MMA(III) on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA(III) concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA(III) induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.
NoteFirst Online: 20 June 2016. 12 month embargo.
VersionFinal accepted manuscript
SponsorsFondo de Apoyo a la Investigacion (FAI), UASLP [C14-FAI-04-10.10]
- The contribution of activated astrocytes to Aβ production: implications for Alzheimer's disease pathogenesis.
- Authors: Zhao J, O'Connor T, Vassar R
- Issue date: 2011 Nov 2
- Exposure to As-, Cd-, and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats.
- Authors: Ashok A, Rai NK, Tripathi S, Bandyopadhyay S
- Issue date: 2015 Jan
- Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models.
- Authors: Lee YJ, Choi DY, Choi IS, Kim KH, Kim YH, Kim HM, Lee K, Cho WG, Jung JK, Han SB, Han JY, Nam SY, Yun YW, Jeong JH, Oh KW, Hong JT
- Issue date: 2012 Feb 19
- Glucocorticoids facilitate astrocytic amyloid-β peptide deposition by increasing the expression of APP and BACE1 and decreasing the expression of amyloid-β-degrading proteases.
- Authors: Wang Y, Li M, Tang J, Song M, Xu X, Xiong J, Li J, Bai Y
- Issue date: 2011 Jul
- Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells.
- Authors: Escudero-Lourdes C, Wu T, Camarillo JM, Gandolfi AJ
- Issue date: 2012 Jan 1