bims-noxint 2021-09-12 papers

Issue of 2021–09–12
three papers selected by
Laia Caja Puigsubira, Uppsala University

Ecotoxicol Environ Saf. 2021 Sep 03. pii: S0147-6513(21)00837-X. [Epub ahead of print]225 112725

NOX2 activation contributes to cobalt nanoparticles-induced inflammatory responses and Tau phosphorylation in mice and microglia.

Jing Li, Junxiang Wang, Yuan-Liang Wang, Zhousong Luo, Chunyan Zheng, Guangxia Yu, Siying Wu, Fuli Zheng, Huangyuan Li.

Despite the wide application of cobalt nanoparticles (CoNPs), its neurotoxicity and the underlying mechanisms are not fully understood. In this study, CoNPs-induced toxic effect was examined in both C57BL/6J mice and microglial BV2 cells. CoNPs-induced brain weight loss and the reduction of Nissl bodies, assuring neural damage. Moreover, both total unphosphorylated Tau and phosphorylated Tau (pTau; T231 and S262) expressions in the hippocampus and cortex were upregulated, unveiling Tau phosphorylation. Besides, the increase in inflammation-related proteins NLRP3 and IL-1β were found in mice brain. Corroborating that, microglial marker Iba-1 expression was also increased, suggesting microglia-involved inflammation. Among the NADPH oxidase (NOX) family proteins tested, only NOX2 was activated by CoNPs in hippocampus. Therefore, BV2 cells were employed to further investigate the role of NOX2. In BV2 cells, NOX2 expression was upregulated, corresponding to the production of ROS. Moreover, similar induction in Tau phosphorylation and inflammation-related protein expressions were observed in CoNPs-exposed BV2 cells. Treatment of apocynin, a NOX2 inhibitor, reduced ROS generation and reversed Tau phosphorylation and inflammation caused by CoNPs. Thus, CoNPs induced ROS production, Tau phosphorylation and inflammation specially via NOX2 activation.

Keywords: CoNPs; Inflammation; Microglia; NOX2; Tau phosphorylation

DOI: https://doi.org/10.1016/j.ecoenv.2021.112725

Commun Biol. 2021 Sep 09. 4(1): 1054

Aβ initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice.

Anton Malkov, Irina Popova, Anton Ivanov, Sung-Soo Jang, Seo Yeon Yoon, Alexander Osypov, Yadong Huang, Yuri Zilberter, Misha Zilberter.

A predominant trigger and driver of sporadic Alzheimer's disease (AD) is the synergy of brain oxidative stress and glucose hypometabolism starting at early preclinical stages. Oxidative stress damages macromolecules, while glucose hypometabolism impairs cellular energy supply and antioxidant defense. However, the exact cause of AD-associated glucose hypometabolism and its network consequences have remained unknown. Here we report NADPH oxidase 2 (NOX2) activation as the main initiating mechanism behind Aβ1-42-related glucose hypometabolism and network dysfunction. We utilize a combination of electrophysiology with real-time recordings of metabolic transients both ex- and in-vivo to show that Aβ1-42 induces oxidative stress and acutely reduces cellular glucose consumption followed by long-lasting network hyperactivity and abnormalities in the animal behavioral profile. Critically, all of these pathological changes were prevented by the novel bioavailable NOX2 antagonist GSK2795039. Our data provide direct experimental evidence for causes and consequences of AD-related brain glucose hypometabolism, and suggest that targeting NOX2-mediated oxidative stress is a promising approach to both the prevention and treatment of AD.

DOI: https://doi.org/10.1038/s42003-021-02551-x

Biotechnol Appl Biochem. 2021 Sep 10.

Long non-coding RNA CASC2 protect ROS-induced Oxidative stress in myocardial infarction by miR-18a/SIRT2.

Guoqiu Ying, Zijun Tang, Jing Zhang, Junyi Zeng, Zeqi Zheng, Wan Zhang, Lu Ding, Tong Wen, Dasong Yi.

BACKGROUND: We aimed to investigate the function and its possible mechanisms of long non-coding RNA (lncRNA) in acute myocardial infarction (AMI) model.
METHODS: Patients with AMI and normal volunteers were collected from our hospital. Sprague Dawley (SD) rats were induced into vivo model of AMI. H9c2 cells were treated with H2O2 to generate injury model.
RESULTS: A significantly lower serum gene expression of lncRNA CASC2 was detected.. In rat models of AMI, lncRNA CASC2 gene expressions in heart tissue of mice with AMI were decreased. In vitro model, down-regulation of lncRNA CASC2 increased reactive oxygen species (ROS) -induced oxidative stress; LncRNA CASC2 induced NADPH oxidase (NOX-2) expression and suppressed miR-18a expression; MiR-18a promoted reactive oxygen species (ROS) -induced oxidative stress; Down-regulation of miR-18a decreased ROS-induced oxidative stress. The inhibition of miR-18a reversed the effects of CASC2 down-regulation on ROS-induced oxidative stress in vitro model of AMI. The activation of miR-18a reversed the effects of CASC2 on ROS-induced oxidative stress in vitro model of AMI.
CONCLUSION: These data for the first time suggest that lncRNA CASC2 have better protective effects on AMI which could be reduce oxidative stress through their carried miR-18a and subsequently down-regulating the SIRT2/ROS pathway. This article is protected by copyright. All rights reserved.

Keywords: ROS; SIRT2; acute myocardial infarction; lncRNA CASC2; miR-18a

DOI: https://doi.org/10.1002/bab.2252