Regulation of NADPH oxidase gene expression with PKA and cytokine IL-4 in neurons and microglia.

Neurotoxicity Research
Valentina L Savchenko

Abstract

Neuronal excitation is mediated by the activation of NMDA receptor and associated with the formation of reactive oxygen species due to the activation of NADPH oxidase complex proteins. The activation of Gs protein coupled receptors (GPCRs) induces neuronal activation in the cAMP-dependent protein kinase A (PKA)-mediated signal cascade and regulates NADPH oxidase activity. However, it is unknown whether PKA regulates NADPH oxidase gene expression in neurons and microglia. In the present research, the NADPH oxidase gene expression was studied in rat cortical neurons and microglia in vitro. Purified microglial cells were identified with OX-42 antibody and they also expressed apolipoprotein E (ApoE). The time-dependent effect of cytokine interleukin-4 (IL-4) (20 ng/ml) in NADPH oxidase gene expression was studied in microglial cells. The levels of mRNA were determined by quantitative RT-PCR. The expression of NOX1, NOX2, and NCF2 was upregulated after IL-4 treatment for 4 h, but it was downregulated after 8-24 h. The expression of NCF1 was suppressed during any time of cytokine effect. IL-4 upregulated arginase1 (Arg1) and serine racemase1 (SRR1) gene expressions in microglia. Amyloid beta (Ab) suppressed NOX2, NCF1, and NCF2 gene ...Continue Reading

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Citations

Dec 19, 2013·Journal of Neuroinflammation·Sean J CooneyKimberly R Byrnes
Sep 18, 2015·Journal of Neuroinflammation·Guzal KhayrullinaKimberly R Byrnes
Sep 25, 2014·Journal of Bioenergetics and Biomembranes·Katrina OwensTibor Kristian
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Feb 11, 2018·Journal of Neuroinflammation·Xiangrong LiuXunming Ji
Jun 9, 2020·Experimental and Therapeutic Medicine·Guoping WangTao Yin
Jan 18, 2017·Molecular Neurodegeneration·Merry W MaDarrell W Brann
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Jan 13, 2016·British Journal of Pharmacology·F VilhardtG McBean
Jun 10, 2019·Journal of Neuroimmunology·Valentyna SavchenkoDouglas L Feinstein

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